PMID:22026371

Citation	Zhang, BW, Brunetti, L and Brooks, CL 3rd (2011) Probing pH-dependent dissociation of HdeA dimers. J. Am. Chem. Soc. 133:19393-8
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.
Links	PubMed PMC3227773 Online version:10.1021/ja2060066
Keywords	Escherichia coli/chemistry; Escherichia coli Proteins/chemistry; Hydrogen-Ion Concentration; Molecular Dynamics Simulation; Protein Multimerization
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