Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 133, Issue 48, Pages 19393-19398Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja2060066
Keywords
-
Categories
Funding
- NIGMS NIH HHS [GM057513, R01 GM057513-11, R01 GM057513] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available