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Probing pH-dependent dissociation of HdeA dimers.

Authors
  • Zhang, Bin W
  • Brunetti, Lucia
  • Brooks, Charles L 3rd
Type
Published Article
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Publication Date
Dec 07, 2011
Volume
133
Issue
48
Pages
19393–19398
Identifiers
DOI: 10.1021/ja2060066
PMID: 22026371
Source
Medline
License
Unknown

Abstract

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 pK(a) values of all the acidic titratable groups in HdeA are obtained and reveal a large pK(a) 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 that the dramatic change in charge on each monomer may drive dissociation. By combining 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.

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