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Probing pH-dependent dissociation of HdeA dimers.

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.

SUBMITTER: Zhang BW

PROVIDER: S-EPMC3227773 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Probing pH-dependent dissociation of HdeA dimers.

Zhang Bin W BW Brunetti Lucia L Brooks Charles L CL

Journal of the American Chemical Society 20111109 48

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 lar ...[more]

PMID: 22026371

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