Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Hi Shane, another curious case is the crystal structure of a signal receiver domain of Desulfovibrio desulfuricans (PDB code: 3cg0, Patskovsky et al., to be published), as discussed in Sippl (2009) Curr. Opin. Struct. Biol. Best, -Markus Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
There is one additional point perhaps worth making: As already noted in the thread, if you have a NCS homo-oligomer, the different copies in general have different environment, and proper inspection of the contacts reveals the details. On multiple occasions during inspections and review I have noticed that such is not always interpreted or welcome as a functionally necessary manifestation of the plasticity of the protein in question. In case of binding sites, in contrast it occurs that the 'best' one where a ligand actually exists or assumes a pose/environment perceived as useful for the proposed hypothesis is picked as the representative (figure), and from there the story evolves. This misses the point, and somewhat reeks of confirmation bias (the neglect of negative or 'unsuitable' results) leading straight down the road to scientific serfdom in terms of becoming a slave of one's own (pre)conceptions Best regards, BR On Wed, Jan 29, 2014 at 10:24 AM, Kay Diederichs kay.diederi...@uni-konstanz.de wrote: Hi Shane, some crystal forms of trimeric AcrB (a multi-drug resistance secondary transporter) have 3 (or 6) monomers in the ASU and these are substantially different, which suggests how the protein functions. One reference is e.g. Seeger et al. (2006) Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism Science 313, 1295-1298 DOI: 10.1126/science.1131542 (sorry for the self-plug!) best, Kay On Mon, 27 Jan 2014 13:08:33 -0500, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University -- - Bernhard Rupp (Hofkristallrat a. D) 001 (925) 209-7429 +43 (676) 571-0536 b...@ruppweb.org hofkristall...@gmail.com http://www.ruppweb.org/ - The hard part about playing chicken is to know when to flinch -
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Insulin can take very different structures for 20% of the residues in different conditions, and there are several examples of T3R3 hexamers, with one T and one R in the asymmetric unit. There are even observations of the transformation occurring within the crystal, which looked battered but still diffracted to some extent. Examples are: 2tci 3mth 1mpj Eleanor Dodson On 30 January 2014 11:06, Bernhard Rupp hofkristall...@gmail.com wrote: There is one additional point perhaps worth making: As already noted in the thread, if you have a NCS homo-oligomer, the different copies in general have different environment, and proper inspection of the contacts reveals the details. On multiple occasions during inspections and review I have noticed that such is not always interpreted or welcome as a functionally necessary manifestation of the plasticity of the protein in question. In case of binding sites, in contrast it occurs that the 'best' one where a ligand actually exists or assumes a pose/environment perceived as useful for the proposed hypothesis is picked as the representative (figure), and from there the story evolves. This misses the point, and somewhat reeks of confirmation bias (the neglect of negative or 'unsuitable' results) leading straight down the road to scientific serfdom in terms of becoming a slave of one's own (pre)conceptions Best regards, BR On Wed, Jan 29, 2014 at 10:24 AM, Kay Diederichs kay.diederi...@uni-konstanz.de wrote: Hi Shane, some crystal forms of trimeric AcrB (a multi-drug resistance secondary transporter) have 3 (or 6) monomers in the ASU and these are substantially different, which suggests how the protein functions. One reference is e.g. Seeger et al. (2006) Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism Science 313, 1295-1298 DOI: 10.1126/science.1131542 (sorry for the self-plug!) best, Kay On Mon, 27 Jan 2014 13:08:33 -0500, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University -- - Bernhard Rupp (Hofkristallrat a. D) 001 (925) 209-7429 +43 (676) 571-0536 b...@ruppweb.org hofkristall...@gmail.com http://www.ruppweb.org/ - The hard part about playing chicken is to know when to flinch -
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Hi Shane, some crystal forms of trimeric AcrB (a multi-drug resistance secondary transporter) have 3 (or 6) monomers in the ASU and these are substantially different, which suggests how the protein functions. One reference is e.g. Seeger et al. (2006) Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism Science 313, 1295-1298 DOI: 10.1126/science.1131542 (sorry for the self-plug!) best, Kay On Mon, 27 Jan 2014 13:08:33 -0500, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
On 27 Jan 2014, at 19:08, Shane Caldwell shane.caldwel...@gmail.com wrote: Here is another interesting one: Perez, C., Koshy, C., Yildiz, Ö., Ziegler, C. (2012). Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP. Nature. best wishes, Tobias Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
In the case of F1-ATPase they are not biologically independent copies in the a.u. though, rather subunits of a biological complex... (but perhaps I interpreted the question to narrowly) Mark J van Raaij Lab 20B Dpto de Estructura de Macromoleculas Centro Nacional de Biotecnologia - CSIC c/Darwin 3 E-28049 Madrid, Spain tel. (+34) 91 585 4616 http://www.cnb.csic.es/~mjvanraaij On 28 Jan 2014, at 05:38, Frank von Delft wrote: F1 ATPase. Got some Nobel glamour too. Sent from tiny silly touch screen - Reply message - From: Aaron Thompson aaron.a.thomp...@gmail.com Date: Tue, Jan 28, 2014 01:10 Subject: [ccp4bb] Examples of multiple ASU copies with different conformations To: CCP4BB@JISCMAIL.AC.UK The structure of kappa opioid receptor fused with T4 lysozyme (4DJH) contains two copies in the ASU – each copy displays a different orientation between the receptor and lysozyme. On Mon, Jan 27, 2014 at 10:08 AM, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
[ccp4bb] AW: [ccp4bb] Examples of multiple ASU copies with different conformations
Dear Shane, Human antithrombin III (code 1ath) is a dimer of an active and latent conformation. Herman Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Shane Caldwell Gesendet: Montag, 27. Januar 2014 19:09 An: CCP4BB@JISCMAIL.AC.UK Betreff: [ccp4bb] Examples of multiple ASU copies with different conformations Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Dear Shane, To add a bit of detail to Frank von Delft's suggestion, perhaps the best example is the structure of the yeast F1-ATPase that has 3 copies in the asu, from David Mueller's lab in Chicago. Two of these are very similar, but the third is rather different and shows a (physiologically relevant) phosphate binding site that is not found in the other two copies. I would not describe the differences as dramatic though. The paper is: Kabaleeswaran et al., EMBO J 25, 5433 (2006) PDB ID 2HLD Best wishes, Andrew Leslie On 27 Jan 2014, at 18:08, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Hi there,
another nice kinase example might be IRAK-4. there are several pdbs,
the one I have in mind is 2OIB. The alphaC helix that takes on
different conformations in active and inactive conformations in
kinases ('in' and 'out') is in four different positions in the four
different copies per asu. A side note is that in this particular
kinase, the helix-out conformation is the active conformation.
Baerbel
On Mon, Jan 27, 2014 at 10:08 AM, Shane Caldwell shane.caldwel...@gmail.com
wrote:
Hi ccp4bb,
I'm putting together a talk for some peers that highlights strengths and
weaknesses of structural models for the outsider. For one point, I'd like
to find some examples of proteins that show very different conformations
between different copies in the ASU. One example I know of is
c-Abl (1OPL),
which crystallizes with both autoinhibited and active forms in the ASU,
with dramatically different domain organization. I'd like to find some
additional examples - can anyone suggest some other structures that have
multiple copies with large structural variations?
Thanks in advance!
Shane Caldwell
McGill University
--
Bärbel Blaum, Ph.D.
Interfakultäres Institut für Biochemie (IFIB)
Hoppe-Seyler-Strasse 4
D-72076 Tübingen
Germany
+49 70 71 29 73 375
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
If you are including two copies in a single biological complex, then the two halves of the reverse transcriptase heterodimer have dramatically different domain organizations (OK, one copy is truncated - losing one whole domain out of five; PDB codes ad nauseam). Indeed one stretch of sequence at the end of domain 4 is extended in one copy and alpha helical in the other.
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Dear Shane, the others have already given very good examples of high impact biology structures; I would still like to add the structure PDB:1J49 (Razeto et al. (2002). JMB 318, 109). Its a structure of a D-Lactate dehydrogenase, a two-domain enzyme, where one ASU subunit adopts an open and the other one a closed conformation - a very interesting case imho. Regards, Fabio Date:Mon, 27 Jan 2014 13:08:33 -0500 From:Shane Caldwell shane.caldwel...@gmail.com Subject: Examples of multiple ASU copies with different conformations Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University -- Dr. rer. nat. Fabio Dall'Antonia European Molecular Biology Laboratory c/o DESY Notkestraße 85, Bldg. 25a D-22603 Hamburg phone: +49 (0)40 89902-178 fax:+49 (0)40 89902-149 e-mail: fabio.dallanto...@embl-hamburg.de
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Hi Shane, One example that comes to mind is aquaporin-z. Two protomers were found in the ASU, one contained the water channel in an open conformation while the other in a closed conformation. The structural differences are not “large” but the functional implication is. Here is the primary citation Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z. Savage DF, Egea PF, Robles-Colmenares Y, O'Connell JD 3rd, Stroud RM. PLoS Biol. 2003 Dec;1(3):E72. Epub 2003 Dec 22. Kind regards Tamir —— gon...@hhmi.org On Jan 27, 2014, at 1:08 PM, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Another interesting example might be a structure of Mad2, protein essential in the process of chromosome segregation. Protein has 2 different secondary structure topologies and both of them are part of the AU in 2V64. There are other X-ray structures where only one of the conformations is captured in the crystal. Good luck, Nikolina Nikolina Sekulic, PhD Research Associate Department of Biochemistry and Biophysics University of Pennsylvania Stellar-Chance Laboratory 912 422 Curie Blvd, Philadelphia cell: 312-437-9095 lab: 215-898-4476 e-mail: seku...@mail.med.upenn.edu On Tue, Jan 28, 2014 at 8:26 AM, tamir gonen tgonen...@gmail.com wrote: Hi Shane, One example that comes to mind is aquaporin-z. Two protomers were found in the ASU, one contained the water channel in an open conformation while the other in a closed conformation. The structural differences are not large but the functional implication is. Here is the primary citation Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z. http://www.ncbi.nlm.nih.gov/pubmed/14691544 *Savage* DF, Egea PF, Robles-Colmenares Y, O'Connell JD 3rd, *Stroud* RM. PLoS Biol. *2003* Dec;1(3):E72. Epub *2003* Dec 22. Kind regards Tamir gon...@hhmi.org On Jan 27, 2014, at 1:08 PM, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
[ccp4bb] Examples of multiple ASU copies with different conformations
Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
The structure of kappa opioid receptor fused with T4 lysozyme (4DJH) contains two copies in the ASU – each copy displays a different orientation between the receptor and lysozyme. On Mon, Jan 27, 2014 at 10:08 AM, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
Hi Shane, One of my favorite examples of large structural differences between molecules in the asymmetric unit have is the crystal structure of the L1 ribozyme (PDB ID 2oiu). The Q and P chains have two stems which crudely co-axially stack and a third stem which appears 180 degrees in the opposite direction between the two molecules in the asymmetric unit. See Figure 2C of the paper: Robertson, M.P. Scott, W.G. The structural basis of ribozyme-catalyzed RNA assembly. Science 2007, 315, 1549-1553; PubMed ID 17363667. Only one conformation appears to be active. Thomas Edwards From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Aaron Thompson Sent: Monday, January 27, 2014 5:11 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Examples of multiple ASU copies with different conformations The structure of kappa opioid receptor fused with T4 lysozyme (4DJH) contains two copies in the ASU - each copy displays a different orientation between the receptor and lysozyme. On Mon, Jan 27, 2014 at 10:08 AM, Shane Caldwell shane.caldwel...@gmail.commailto:shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
Re: [ccp4bb] Examples of multiple ASU copies with different conformations
F1 ATPase. Got some Nobel glamour too. Sent from tiny silly touch screen - Reply message - From: Aaron Thompson aaron.a.thomp...@gmail.com Date: Tue, Jan 28, 2014 01:10 Subject: [ccp4bb] Examples of multiple ASU copies with different conformations To: CCP4BB@JISCMAIL.AC.UK The structure of kappa opioid receptor fused with T4 lysozyme (4DJH) contains two copies in the ASU – each copy displays a different orientation between the receptor and lysozyme. On Mon, Jan 27, 2014 at 10:08 AM, Shane Caldwell shane.caldwel...@gmail.com wrote: Hi ccp4bb, I'm putting together a talk for some peers that highlights strengths and weaknesses of structural models for the outsider. For one point, I'd like to find some examples of proteins that show very different conformations between different copies in the ASU. One example I know of is c-Abl (1OPL), which crystallizes with both autoinhibited and active forms in the ASU, with dramatically different domain organization. I'd like to find some additional examples - can anyone suggest some other structures that have multiple copies with large structural variations? Thanks in advance! Shane Caldwell McGill University
