3AGZ

Crystal structure of human Hsp40 Hdj1 peptide-binding domain complexed with a C-terminal peptide of Hsp70

Summary for 3AGZ

• Entry DOI: 10.2210/pdb3agz/pdb
• Related: 3AGX 3AGY
• Descriptor: DnaJ homolog subfamily B member 1, peptide of Heat shock cognate 71 kDa protein (3 entities in total)
• Functional Keywords: chaperone
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P25685 P11142
• Total number of polymer chains: 6
• Total formula weight: 46391.55

Authors

Suzuki, H.,Noguchi, S.,Satow, Y. (deposition date: 2010-04-12, release date: 2011-02-23, Last modification date: 2024-03-13)

Primary citation

Suzuki, H.,Noguchi, S.,Arakawa, H.,Tokida, T.,Hashimoto, M.,Satow, Y.
Peptide-binding sites as revealed by the crystal structures of the human Hsp40 Hdj1 C-terminal domain in complex with the octapeptide from human Hsp70
Biochemistry, 49:8577-8584, 2010

PubMed Abstract: Heat shock protein (Hsp) 40s play essential roles in cellular processes by cooperating with Hsp70 proteins. Hsp40 proteins recognize non-native polypeptides, deliver these peptides to Hsp70 proteins, and stimulate the ATPase activity of Hsp70 proteins to facilitate the correct folding of the polypeptides. We have determined the crystal structures of the C-terminal peptide-binding domain of human Hsp40 Hdj1 (CTD) and of its complex with the C-terminal octapeptide of human Hsp70, (634')GPTIEEVD(641'). CTD exists as a twisted, horseshoe-shaped homodimer. The protomer consists of two domains, I and II, with similar topologies. The octapeptides are located in two sites, 1 and 2, of domain I. In site 1, the octapeptide forms an antiparallel β-sheet with CTD. The negatively charged residues of the EEVD motif in the octapeptide form electrostatic interactions with the positively charged Lys residues of CTD. The Ile side chain of the octapeptide fits into the narrow concave formed by the hydrophobic residues of CTD. In site 2, the octapeptide also forms an antiparallel β-sheet with CTD, and the EEVD motif forms electrostatic interactions. The side chains of Pro and Ile of the octapeptide interact with the hydrophobic surface region of CTD site 2, which is broader and shallower than the concave binding region of site 1. This region seems to be capable of binding hydrophobic side chains that are bulkier than the Ile side chain. The roles of these two peptide-binding sites of Hdj1 are discussed.

PubMed: 20809635
DOI: 10.1021/bi100876n

Experimental method

X-RAY DIFFRACTION (2.51 Å)