Salt Bridges Regulate Both Dimer Formation and Monomeric Flexibility in HdeB and May Have a Role in Periplasmic Chaperone Function

JOURNAL OF MOLECULAR BIOLOGY

卷:415

Article

Wang, Wenjian^2,3  Rasmussen, Tim¹  Harding, Amanda J.¹  Booth, Nuala A.¹  Booth, Ian R.¹  Naismith, James H.² 

[1] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland

[2] Univ St Andrews, St Andrews KY16 9ST, Fife, Scotland

[3] Sun Yat Sen Univ, Lab Dept Surg, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China

关键词: crystal structure;    fluorescence measurements;    hydrophobic residues;    acid response;    pH titration;   

DOI  :  10.1016/j.jmb.2011.11.026

来源: Elsevier

【 摘 要 】

Escherichia coli and Gram-negative bacteria that live in the human gut must be able to tolerate rapid and large changes in environmental pH. Low pH irreversibly denatures and precipitates many bacterial proteins. While cytoplasmic proteins are well buffered against such swings, periplasmic proteins are not. Instead, it appears that some bacteria utilize chaperone proteins that stabilize periplasmic proteins, preventing their precipitation. Two highly expressed and related proteins, HdeA and HdeB, have been identified as acid-activated chaperones. The structure of HdeA is known and a mechanism for activation has been proposed. In this model, dimeric HdeA dissociates at low pH, and the exposed dimeric interface binds exposed hydrophobic surfaces of acid-denatured proteins, preventing their irreversible aggregation. We now report the structure and biophysical characterization of the HdeB protein. The monomer of HdeB shares a similar structure with HdeA, but its dimeric interface is different in composition and spatial location. We have used fluorescence to study the behavior of HdeB as pH is lowered, and like HdeA, it dissociates to monomers. We have identified one of the key intersubunit interactions that controls pH-induced monomerization. Our analysis identifies a structural interaction within the HdeB monomer that is disrupted as pH is lowered, leading to enhanced structural flexibility. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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