Document Detail


Probing pH-dependent Dissociation of HdeA Dimers.
MedLine Citation:
PMID:  22026371     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
HdeA protein is a small, ATP-independent, acid stress chaperone that undergoes a dimer- to-monomer transition in acidic environments. The HdeA monomer binds a broad range of proteins to prevent their acid-induced aggregation. To understand better HdeA's function and mechanism, we perform constant-pH molecular dynamics simulations (CPHMD) to elucidate the details of the HdeA dimer dissociation process. First the pKa values of all the acidic titrat- able groups in HdeA are obtained and reveal a large pKa shift only for Glu(37). However, the pH-dependent monomer charge exhibits a large shift from -4 at pH > 6 to +6 at pH = 2.5, suggesting the dramatic change in charge on each monomer may drive dissociation. By com- bining the CPHMD approach with umbrella sampling, we demonstrate a significant stability decrease of the HdeA dimer when the environmental pH changes from 4.0 to 3.5, and identify the key acidic residue - lysine interactions responsible for the observed pH sensing in HdeA chaperon activity function.
Authors:
Bin W Zhang; Lucia Brunetti; Charles Lee Brooks
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-25
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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