The Crystal Structure of the Putative Peptide-binding Fragment from the Human Hsp40 Protein Hdj1

Overview

Journal BMC Struct Biol

Publisher Biomed Central

Specialties Biochemistry
Molecular Biology

Date 2008 Jan 24

PMID 18211704

Citations 23

Authors

Junbin Hu

Yunkun Wu

Jingzhi Li

Xinguo Qian

Zhengqing Fu

Bingdong Sha

Affiliations

Soon will be listed here.

Abstract

Background: The mechanism by which Hsp40 and other molecular chaperones recognize and interact with non-native polypeptides is a fundamental question. How Hsp40 co-operates with Hsp70 to facilitate protein folding is not well understood. To investigate the mechanisms, we determined the crystal structure of the putative peptide-binding fragment of Hdj1, a human member of the type II Hsp40 family.

Results: The 2.7A structure reveals that Hdj1 forms a homodimer in the crystal by a crystallographic two-fold axis. The Hdj1 dimer has a U-shaped architecture and a large cleft is formed between the two elongated monomers. When compared with another Hsp40 Sis1 structure, the domain I of Hdj1 is rotated by 7.1 degree from the main body of the molecule, which makes the cleft between the two Hdj1 monomers smaller that that of Sis1.

Conclusion: This structural observation indicates that the domain I of Hsp40 may possess significant flexibility. This flexibility may be important for Hsp40 to regulate the size of the cleft. We propose an "anchoring and docking" model for Hsp40 to utilize the flexibility of domain I to interact with non-native polypeptides and transfer them to Hsp70.

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