Re: [ccp4bb] do you think it is interesting?
On 06/20/12 00:36, Edward A. Berry wrote: Sorry to come late to this discussion- I think the actin and tubulin people already reverted polymer to its etymological use- google actin polymerization True. Objections withdrawn. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
Sorry to come late to this discussion- I think the actin and tubulin people already reverted polymer to its etymological use- google actin polymerization Another example of infinite polymers formed by domain swapping (and the surprises you can get trying to engineer a molecular switch): http://www.ncbi.nlm.nih.gov/pubmed/22245575 eab Jacob Keller wrote: Okay, I wiki'd it, and according to them seems you're right: it says they are typically connected by covalent chemical bonds. So either we revert to the etymological use of polymer, or move onward to myriomer! (assuming the cross-bred multimer is out of the question!) JPK On Mon, Jun 18, 2012 at 10:37 AM, David Schullerdj...@cornell.edu wrote: On 06/18/12 11:17, Jacob Keller wrote: But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? subtle? No, it's not subtle. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
Wow, that's very cool! Can you divulge what the function of the protein is? One thinks of some kind of mechanical spring... JPK On Mon, Jun 18, 2012 at 8:49 AM, anna anna marmottalb...@gmail.com wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] do you think it is interesting?
Certainly it's interesting, but I think your description is inaccurate. Endless linear polymers - Each monomer is a polymer, but a collection of monomers is called a multimer, not a polymer. I don't suppose there are any knots? That would be really interesting. On 06/18/12 09:49, anna anna wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
-BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. Cheers, Tim On 06/18/12 16:21, David Schuller wrote: Certainly it's interesting, but I think your description is inaccurate. Endless linear polymers - Each monomer is a polymer, but a collection of monomers is called a multimer, not a polymer. I don't suppose there are any knots? That would be really interesting. On 06/18/12 09:49, anna anna wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP3z51UxlJ7aRr7hoRAqviAKDJXxXkeOE3Z0M14+RT8dznQhpD3gCcDKEP o034eyZnadpwyQRGXI4FV9w= =Q5GJ -END PGP SIGNATURE-
Re: [ccp4bb] do you think it is interesting?
how about greek-protomers-bands (aka GPB) :-) Nice picture, you can make decorative art with it and sell it. Jürgen On Jun 18, 2012, at 10:43 AM, Tim Gruene wrote: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. Cheers, Tim On 06/18/12 16:21, David Schuller wrote: Certainly it's interesting, but I think your description is inaccurate. Endless linear polymers - Each monomer is a polymer, but a collection of monomers is called a multimer, not a polymer. I don't suppose there are any knots? That would be really interesting. On 06/18/12 09:49, anna anna wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP3z51UxlJ7aRr7hoRAqviAKDJXxXkeOE3Z0M14+RT8dznQhpD3gCcDKEP o034eyZnadpwyQRGXI4FV9w= =Q5GJ -END PGP SIGNATURE- .. Jürgen Bosch Johns Hopkins University Bloomberg School of Public Health Department of Biochemistry Molecular Biology Johns Hopkins Malaria Research Institute 615 North Wolfe Street, W8708 Baltimore, MD 21205 Office: +1-410-614-4742 Lab: +1-410-614-4894 Fax: +1-410-955-2926 http://web.mac.com/bosch_lab/
Re: [ccp4bb] do you think it is interesting?
On 06/18/12 10:43, Tim Gruene wrote: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. I didn't invent the term multimer, it has been in use for some decades. And I am writing English, not Latin or Greek. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
I have been curious and suspicious for a long time about multimer: I always assumed it to be a more homey substitute for oligomer, as there seems to me to be no difference in usage, and certainly not in the etymological sense. I have often heard it used by non-experts who don't know exactly the meaning of the prefix oligo- but do know multi-, so they feel more comfortable I think. But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? JPK On Mon, Jun 18, 2012 at 9:48 AM, David Schuller dj...@cornell.edu wrote: On 06/18/12 10:43, Tim Gruene wrote: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. I didn't invent the term multimer, it has been in use for some decades. And I am writing English, not Latin or Greek. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] do you think it is interesting?
Of course, oligomer (pure Greek) usually does that kind of job, but not in this specific case, since oligo means few and in this case we have endless chains. I can only think of the neologism myriomer for this particular case, if you want to stick to Greek. Myrioi can mean 1 or countless, depending on where you accent the word! If that catches on, remember you (probably) saw it here first! Cheers, Emmanuel - Original Message - From: Tim Gruene t...@shelx.uni-ac.gwdg.de To: CCP4BB@JISCMAIL.AC.UK Sent: Monday, June 18, 2012 5:43 PM Subject: Re: [ccp4bb] do you think it is interesting? -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. Cheers, Tim On 06/18/12 16:21, David Schuller wrote: Certainly it's interesting, but I think your description is inaccurate. Endless linear polymers - Each monomer is a polymer, but a collection of monomers is called a multimer, not a polymer. I don't suppose there are any knots? That would be really interesting. On 06/18/12 09:49, anna anna wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP3z51UxlJ7aRr7hoRAqviAKDJXxXkeOE3Z0M14+RT8dznQhpD3gCcDKEP o034eyZnadpwyQRGXI4FV9w= =Q5GJ -END PGP SIGNATURE-
Re: [ccp4bb] do you think it is interesting?
On 18/06/2012, Tim Gruene t...@shelx.uni-ac.gwdg.de wrote: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. Cheers, Tim Oligomer, surely, from Gk 'oligos' meaning 'a few'? -- Ian
Re: [ccp4bb] do you think it is interesting?
On 06/18/12 11:17, Jacob Keller wrote: But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? subtle? No, it's not subtle. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
I love myriomer, but what's wrong with boring old polymer? JPK On Mon, Jun 18, 2012 at 10:27 AM, Emmanuel Saridakis esari...@chem.demokritos.gr wrote: Of course, oligomer (pure Greek) usually does that kind of job, but not in this specific case, since oligo means few and in this case we have endless chains. I can only think of the neologism myriomer for this particular case, if you want to stick to Greek. Myrioi can mean 1 or countless, depending on where you accent the word! If that catches on, remember you (probably) saw it here first! Cheers, Emmanuel - Original Message - From: Tim Gruene t...@shelx.uni-ac.gwdg.de To: CCP4BB@JISCMAIL.AC.UK Sent: Monday, June 18, 2012 5:43 PM Subject: Re: [ccp4bb] do you think it is interesting? -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. Cheers, Tim On 06/18/12 16:21, David Schuller wrote: Certainly it's interesting, but I think your description is inaccurate. Endless linear polymers - Each monomer is a polymer, but a collection of monomers is called a multimer, not a polymer. I don't suppose there are any knots? That would be really interesting. On 06/18/12 09:49, anna anna wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP3z51UxlJ7aRr7hoRAqviAKDJXxXkeOE3Z0M14+RT8dznQhpD3gCcDKEP o034eyZnadpwyQRGXI4FV9w= =Q5GJ -END PGP SIGNATURE- -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] do you think it is interesting?
Okay, I wiki'd it, and according to them seems you're right: it says they are typically connected by covalent chemical bonds. So either we revert to the etymological use of polymer, or move onward to myriomer! (assuming the cross-bred multimer is out of the question!) JPK On Mon, Jun 18, 2012 at 10:37 AM, David Schuller dj...@cornell.edu wrote: On 06/18/12 11:17, Jacob Keller wrote: But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? subtle? No, it's not subtle. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] do you think it is interesting?
isn't a polymer considered a poly-multimer of undefined size ? And you use multi once you run out with your greek naming scheme say when icosahedron ? Jürgen P.S. where are all those greeks to shed some light on us ? On Jun 18, 2012, at 11:48 AM, Jacob Keller wrote: Okay, I wiki'd it, and according to them seems you're right: it says they are typically connected by covalent chemical bonds. So either we revert to the etymological use of polymer, or move onward to myriomer! (assuming the cross-bred multimer is out of the question!) JPK On Mon, Jun 18, 2012 at 10:37 AM, David Schuller dj...@cornell.edumailto:dj...@cornell.edu wrote: On 06/18/12 11:17, Jacob Keller wrote: But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? subtle? No, it's not subtle. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edumailto:schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edumailto:j-kell...@northwestern.edu *** .. Jürgen Bosch Johns Hopkins University Bloomberg School of Public Health Department of Biochemistry Molecular Biology Johns Hopkins Malaria Research Institute 615 North Wolfe Street, W8708 Baltimore, MD 21205 Office: +1-410-614-4742 Lab: +1-410-614-4894 Fax: +1-410-955-2926 http://web.mac.com/bosch_lab/
Re: [ccp4bb] do you think it is interesting?
If the original poster could engineer a few disulfides or other covalent linkages in there, I would drop my objections, and be even more impressed. On 06/18/12 11:48, Jacob Keller wrote: Okay, I wiki'd it, and according to them seems you're right: it says they are typically connected by covalent chemical bonds. So either we revert to the etymological use of polymer, or move onward to myriomer! (assuming the cross-bred multimer is out of the question!) JPK On Mon, Jun 18, 2012 at 10:37 AM, David Schullerdj...@cornell.edu wrote: On 06/18/12 11:17, Jacob Keller wrote: But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? subtle? No, it's not subtle. -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
If we are to strictly adhere to polymer as describing few, then were do we stand with DNA/RNA being described as a polymer - a long polymer made up from repeating units of nucleotides, as has been used in textbooks for ages?! Is DNA/RNA too now a myriomer? Cale
Re: [ccp4bb] do you think it is interesting?
Hi Anna, Interesting assembly. What is the function of your protein? Is it known if your protein forms a fibril-like assembly in solution? Moreover, can your crystal packing be indexed higher symmetry space group? Cheers, Shiva On Mon, Jun 18, 2012 at 9:03 AM, David Schuller dj...@cornell.edu wrote: If the original poster could engineer a few disulfides or other covalent linkages in there, I would drop my objections, and be even more impressed. On 06/18/12 11:48, Jacob Keller wrote: Okay, I wiki'd it, and according to them seems you're right: it says they are typically connected by covalent chemical bonds. So either we revert to the etymological use of polymer, or move onward to myriomer! (assuming the cross-bred multimer is out of the question!) JPK On Mon, Jun 18, 2012 at 10:37 AM, David Schullerdj...@cornell.edu wrote: On 06/18/12 11:17, Jacob Keller wrote: But anyway, what is wrong with calling her structures polymers? Is there a subtle covalent insinuation to polymer? subtle? No, it's not subtle. -- ==**==** === All Things Serve the Beam ==**==** === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- ==**==** === All Things Serve the Beam ==**==** === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu
Re: [ccp4bb] do you think it is interesting?
2012/6/18 Tim Gruene t...@shelx.uni-ac.gwdg.de: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 [...] of monomers is called a multimer, not a polymer. [...] shiver - what a terrible mixture of languages. 'multi-' has got latin origin, whereas both poly and mer have got greek origin, and I don't think one should mix these. Please!!! think of a different _GREEK_ syllable to express what you describe as 'multimer'. In fact this is quite common. Automobile, for example comes from greek autos plus latin mobilis.
Re: [ccp4bb] do you think it is interesting?
This may be somethng similar Domain swapping of a llama VHH domain builds a crystal-wide beta-sheet structure. Spinelli S, Desmyter A, Frenken L, Verrips T, Tegoni M, Cambillau C. FEBS Lett. 2004 Apr 23;564(1-2):35-40. Remy Loris Vrije Universiteit Brussel On 18/06/12 15:49, anna anna wrote: Hi all! I'd like your opinion about a structure I solved. Apart from protein structure itself, I think that my protein xtallized in an odd way! The biological unit is a dimer while the asymmetric unit is a tetramer (red cartoon in the figure) resulting from domain swapping between two dimers. The strange thing is that swapping connects infinite monomers and, rather than a xtal, my diffracting object seems a multilayer of endless linear polymers, a kind of papyrus with greek fret-like fibers. The figure shows the orientation of the polymers in each layer. I'd like to know if some of you have already seen a similar pattern or it is weird as I think! I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. All suggestions are welcome!! Cheers, Anna
Re: [ccp4bb] do you think it is interesting?
I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. There are a variety of domain swapped crystal structures out there, but at least the two I'm most familiar with are regarded as being crystallization artifacts. I think I recall seeing examples where domain swapping was biologically relevant, but my impression is most are red herrings. In the poster child of plaque formation, prion protein formed cys-cross linked domain swapped dimers in some crystals. http://www.nature.com/nsmb/journal/v8/n9/abs/nsb0901-770.html However, using PAGE DLS it was later shown that prion has no preference for dimers when you break down Infectious fibrils. Cross linked dimers definitely out. Any subunits ruled out, in fact. http://www.nature.com/nature/journal/v437/n7056/abs/nature03989.html RNaseA is another example, and isn't even a disease associated molecule. Similarly to how we've found that many/most proteins may be converted to amyloid forms by harsh enough conditions, I think some will domain swap, and some authors have pursued domain swapping heavily with RNaseA a as a model for amyloid formation. RNaseA will swap in major and minor conformations even, though not in the same crystal. Still, that's the first thing you need for an infinite series, is two compatible/simultaneous swapping points. Now, I do think domain swapping, particularly an infinite chain, can be interesting from a bioengineering or biophysical level, if that is what you are interested in. I just want to say that there is a high bar to showing biochemical relevance in the sense of holding any physiological implications. Alexander D. Scouras Postdoctoral Fellow Alber Lab, QB3 University of California, Berkeley
Re: [ccp4bb] do you think it is interesting?
I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. A good example of domain swaps involved in disease-associated polymerisation is the polymerisation of serpins; while there is still some debate about whether this mechanism is actually what happens in patients in vivo, the formation of polymers via domain swapping is becoming widely accepted as the new paradigm. Relevant references include: Nature. 2008 Oct 30;455(7217):1255-8. Epub 2008 Oct 15. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Yamasaki M, Li W, Johnson DJ, Huntington JA. PMID: 18923394 EMBO Rep. 2011 Sep 30;12(10):1011-7. doi: 10.1038/embor.2011.171. Molecular basis of α1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. Yamasaki M, Sendall TJ, Pearce MC, Whisstock JC, Huntington JA. PMID: 21909074 Interestingly enough they don't rely on disulfide formation (normal polymers fall apart on an SDS gel but not a native gel), but they can be engineered to include disulfides which render the polymers stable to SDS (on a non-reducing gel). This was actually a really useful tool in determining exactly which domains of a given molecule swapped into their neighbour during polymerisation. Best Regards Tom
Re: [ccp4bb] do you think it is interesting?
On Monday, June 18, 2012 02:06:46 pm Alexander Scouras wrote: I'm further racking my brain to figure out a biological implication of this behaviour, I thought something like plaque formation but I can't find support in literature. There are a variety of domain swapped crystal structures out there, but at least the two I'm most familiar with are regarded as being crystallization artifacts. I think I recall seeing examples where domain swapping was biologically relevant, but my impression is most are red herrings. You might be interested in the following paper, which describes domain-swapped (domain exchange) dimerization as a control mechanism for kinases. Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites. Pike, A.C.W., Rellos, P., Niesen, F.H., Turnbull, A., Oliver, A.W., Parker, S.A., Turk, B.E., Pearl, L.H., Knapp, S., Journal: (2008) Embo J. 27: 704 But these are specifically dimeric. Unlike the case posted here, there is not a second non-swapped interface that would allow formation of an infinite chain. Ethan In the poster child of plaque formation, prion protein formed cys-cross linked domain swapped dimers in some crystals. http://www.nature.com/nsmb/journal/v8/n9/abs/nsb0901-770.html However, using PAGE DLS it was later shown that prion has no preference for dimers when you break down Infectious fibrils. Cross linked dimers definitely out. Any subunits ruled out, in fact. http://www.nature.com/nature/journal/v437/n7056/abs/nature03989.html RNaseA is another example, and isn't even a disease associated molecule. Similarly to how we've found that many/most proteins may be converted to amyloid forms by harsh enough conditions, I think some will domain swap, and some authors have pursued domain swapping heavily with RNaseA a as a model for amyloid formation. RNaseA will swap in major and minor conformations even, though not in the same crystal. Still, that's the first thing you need for an infinite series, is two compatible/simultaneous swapping points. Now, I do think domain swapping, particularly an infinite chain, can be interesting from a bioengineering or biophysical level, if that is what you are interested in. I just want to say that there is a high bar to showing biochemical relevance in the sense of holding any physiological implications. Alexander D. Scouras Postdoctoral Fellow Alber Lab, QB3 University of California, Berkeley -- Ethan A Merritt Biomolecular Structure Center, K-428 Health Sciences Bldg University of Washington, Seattle 98195-7742
Re: [ccp4bb] do you think it is interesting?
Hi Anna, Your structure and description remind me very much of our domain-swapped crystal structure of trp repressor, also an infinite lattice. One more example to add to the many that have been pointed out by others. http://www.pdb.org/pdb/explore.do?structureId=1MI7 Cheers, Cathy Lawson