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J Phys Chem B. 2013 Oct 24;117(42):13219-25. doi: 10.1021/jp403264s. Epub 2013 Jul 1.

Binding and folding of the small bacterial chaperone HdeA.

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1
Department of Chemistry, The University of Michigan , Ann Arbor, Michigan, United States.

Abstract

The small pH stress-sensing chaperone HdeA helps pathogenic enteric E. coli survive passage through the severely acidic environment of the mammalian stomach. Under stress conditions, HdeA transitions from an inactive folded dimer to a chaperone-active unfolded monomer to prevent the acid-induced aggregation of periplasmic proteins. Here we use a topology-based Gō-like model to delineate the relationship between dimer interface formation and monomer folding and to better understand the structural details of the chaperone activation mechanism. Free energy surfaces show that dimer interface formation and monomer folding proceed concurrently through an on-pathway dimeric intermediate in which one monomer is partially unfolded. The absence of a preexisting fully folded monomer in the proposed binding mechanism is in agreement with HdeA's rapid chaperone response. Binding between unfolded monomers exhibits an enhancement of molecular recognition reminiscent of the fly-casting mechanism. Overall, our simulations further highlight the efficient nature of HdeA's chaperone response and we anticipate that knowledge of a dimeric intermediate will facilitate the interpretation of experimental studies.

PMID:
23738772
PMCID:
PMC3808462
DOI:
10.1021/jp403264s
[Indexed for MEDLINE]
Free PMC Article
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