Document Detail


Separating instability from aggregation propensity in γS-crystallin variants.
MedLine Citation:
PMID:  21244846     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular dynamics (MD) simulations, circular dichroism (CD), and dynamic light scattering (DLS) measurements were used to investigate the aggregation propensity of the eye-lens protein γS-crystallin. The wild-type protein was investigated along with the cataract-related G18V variant and the symmetry-related G106V variant. The MD simulations suggest that local sequence differences result in dramatic differences in dynamics and hydration between these two apparently similar point mutations. This finding is supported by the experimental measurements, which show that although both variants appear to be mostly folded at room temperature, both display increased aggregation propensity. Although the disease-related G18V variant is not the most strongly destabilized, it aggregates more readily than either the wild-type or the G106V variant. These results indicate that γS-crystallin provides an excellent model system for investigating the role of dynamics and hydration in aggregation by locally unfolded proteins.
Authors:
William D Brubaker; J Alfredo Freites; Kory J Golchert; Rebecca A Shapiro; Vasilios Morikis; Douglas J Tobias; Rachel W Martin
Related Documents :
24987416 - Vitamin d binding protein and bone health.
9033846 - Partial purification of the pig kidney cystic fibrosis transmembrane regulator protein.
123776 - Dynamic affinity chromatography of heavy meromyosin subfragment-1.
23075246 - Association of decreased serum protein fractions with clostridium difficile infection i...
24006436 - Outer membrane proteins ail and ompf of yersinia pestis are involved in the adsorption ...
23846 - Solubilization and partial characterization of a phosphoprotein phosphatase from human ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biophysical journal     Volume:  100     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-19     Completed Date:  2011-04-25     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  498-506     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Molecular Biology and Biochemistry, University of California, Irvine, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cataract / genetics,  pathology
Circular Dichroism
Crystallins / chemistry*,  genetics*
Humans
Molecular Dynamics Simulation*
Point Mutation*
Protein Conformation
Protein Denaturation
Protein Folding
gamma-Crystallins / chemistry*,  genetics*
Grant Support
ID/Acronym/Agency:
GM86685/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Crystallins; 0/gamma-Crystallins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Force spectroscopy of substrate molecules en route to the proteasome's active sites.
Next Document:  A nonfitting method using a spatial sine window transform for inhomogeneous effective-diffusion meas...