Dear Intekhab

Let me just add to this that gel filtration is not an accurate method for
determination of molecular mass, because the migration on the column depends
on the shape of the protein.

The following methods can be used to determine molecular mass irrespective
of shape:
- MALLS (multi-angle laser light scattering or static light sxattering)
- sedimentation equilibrium on analytical ultracentrifuge (AUC)
- native mass spectrometry

For a short recent review on issues associated with determining oligomeric
state from crystal structures, with older references and relevant
bioinformatic tools cited in there, please see
http://www.ncbi.nlm.nih.gov/pubmed/19021571

Bostjan


On 10/08/10 6:26 AM, "Maia Cherney" <[email protected]> wrote:

> To determine the oligomeric state of a protein (monomer or dimer in your
> case), it's useful to use the PISA server. You upload your pdb file from
> the crystal structure.The server calculates the areas of interfaces
> (buried area) and  deltaG (change in Gibbs energy) upon oligomer
> dissociation. (E. Krissinel and K. Henrick (2007). /Inference of
> macromolecular assemblies from crystalline state/. J. Mol. Biol. *372*,
> 774--797 . E. Krissinel and K. Henrick (2005). /Detection of Protein
> Assemblies in Crystals/. In: M.R. Berthold /et.al./ (Eds.): CompLife
> 2005, LNBI 3695, pp. 163--174 <http://dx.doi.org/10.1007/11560500_15>.
> E. Krissinel (2009). /Crystal contacts as nature's docking solutions/.
> J. Comp. Chem., in press; published on-line 6 May 2009; DOI
> 10.1002/jcc.21303}
> If the interface area (divided by 2 per one protomer) is greater than
> 1000 A2 and delta G is more than 5kcal/mol (the higher the better), it's
> a dimer. However, don't forget that most dimers can dissociate into
> monomers upon dilution. There is a dynamic equilibrium between dimers
> (oligomers) and monomers that depends on their concentration and the Kdiss.
> Separating them in any method will disturb this equilibrium. If the
> re-equilibration time is greater than the separation time, you can see
> both monomers and dimers. You can even roughly calculate the
> dissociation constant:
> 
> Kdiss=[monomer]2/[dimer] where brackets mean concentrations. To give you
> an estimate, at Kdiss=10(-3)M, you have roughly equal concentration of
> dimers and monomers at 10-3 M and only 10% dimers at 10-4 M. Sometimes,
> protein needs to dissociate easily for the biological function.
> 
> Maia
> 
> intekhab alam wrote:
>> Hi everyone
>> Sorry for some non specific query!!!!!
>>  
>> i am working with a protein that shows a dimer in the crystal
>> structure but when i tried to figure out that with standard molecular
>> markers in gel filteration (superdex-200, 24ml column) it turned out
>> to be a monnomer. Native gel analysis after incubating the protein at
>> 20 degree, 37 degree showed more dimer at 20 degree celcius as
>> compared to 37. I tried similar strategy in gel filteration by
>> incubating my protein at various temperature,where a lot of
>> precipitation was observed at 37 degree celcius and after removing the
>> precipitates i run the gel filteration that has 0.5 ml higher elution
>> volume as compared to samples incubated at 20 degree celcius and 4
>> degree celcius.( Is this significant)
>> Furthermore i have done some experiments in cold room (4 degree) where
>> the elution volume is stuck at a point irrespective of the conditions
>> (as Flow rate, concentration of protein etc) and that is higher than
>> that of the room temperature by 1 ml.
>> Standard moleculr weight markers also show higher elution volume  in
>> cold room in comparison to the room temperature by 1 ml.
>>  
>> I will be highly obliged if someone suggest some literature  or any
>> otherway to do gel filtrtaion so that i can clearly resolve this
>> issue. Also let me know if there is some literature
>> available on effect of temperature on the elution volume of proteins.
>>  
>> Thanks in advance
>>  
>> -- 
>> INTEKHAB ALAM
>> LABORATORY OF STRUCTURAL BIOINFORMATICS
>> KOREA UNIVERSITY, SEOUL

---
Bostjan Kobe
ARC Federation Fellow
Professor of Structural Biology
School of Chemistry and Molecular Biosciences
> and Institute for Molecular Bioscience (Division of Chemistry and Structural
> Biology) and Centre for Infectious Disease Research
Cooper Road
University of Queensland
Brisbane, Queensland 4072
Australia
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E-mail: [email protected]
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