Related Experiment Videos
Residues participating in the protein folding nucleus do not exhibit preferential evolutionary conservation
Stefan M Larson1, Ingo Ruczinski, Alan R Davidson
1Department of Chemistry and Biophysics Program, Stanford University, Stanford, CA 94305, USA.
Journal of Molecular Biology
|February 20, 2002
Summary
Natural selection does not appear to optimize protein folding nuclei residues for evolutionary conservation. Existing data shows experimental bias, not preferential conservation of these key protein folding residues.
Area of Science:
- Biochemistry
- Molecular Biology
- Evolutionary Biology
Background:
- Investigating natural selection's role in optimizing protein folding kinetics is crucial.
- Previous studies lack consensus on the evolutionary conservation of residues in protein folding nuclei.
Purpose of the Study:
- To systematically investigate sequence conservation in experimentally defined protein folding nuclei.
- To determine if residues in the folding nucleus exhibit anomalous evolutionary conservation.
Main Methods:
- Exhaustive, systematic study of sequence conservation.
- Analysis of experimentally (Phi-value) defined folding nuclei across characterized proteins.
- Comparison of conservation in folding nucleus residues versus other kinetically characterized residues.
Main Results:
- No significant evidence of anomalous sequence conservation in folding nucleus residues was found.
- A bias in existing kinetic data showed higher conservation in studied residues than overall residues.
- Correcting for this bias eliminated the previously reported preferential conservation.
Conclusions:
- Natural selection does not seem to preferentially conserve residues within protein folding nuclei.
- Both poorly and highly conserved residues are equally likely to be part of the protein-folding nucleus.
- Existing observations of preferential conservation are attributed to systematic experimental bias.