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Title: 2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix

Abstract

TRAP1 is an organelle-specific Hsp90 paralog that is essential for neoplastic growth. As a member of the Hsp90 family, TRAP1 is presumed to be a general chaperone facilitating the late-stage folding of Hsp90 client proteins in the mitochondrial matrix. Interestingly, TRAP1 cannot replace cytosolic Hsp90 in protein folding, and none of the known Hsp90 co-chaperones are found in mitochondria. Thus, the three-dimensional structure of TRAP1 must feature regulatory elements that are essential to the ATPase activity and chaperone function of TRAP1. Here, the crystal structure of a human TRAP1 NMdimer is presented, featuring an intact N-domain and M-domain structure, bound to adenosine 5'-β,γ-imidotriphosphate (ADPNP). The crystal structure together with epitope-mapping results shows that the TRAP1 M-domain loop 1 contacts the neighboring subunit and forms a previously unobserved third dimer interface that mediates the specific interaction with mitochondrial Hsp70.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)
OSTI Identifier:
1337160
DOE Contract Number:
AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D. Structural Biology; Journal Volume: 72; Journal Issue: 8
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; Hsp90 paralog; TRAP1; mitochondrial matrix; molecular chaperones

Citation Formats

Sung, Nuri, Lee, Jungsoon, Kim, Ji-Hyun, Chang, Changsoo, Tsai, Francis T. F., and Lee, Sukyeong. 2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix. United States: N. p., 2016. Web. doi:10.1107/S2059798316009906.
Sung, Nuri, Lee, Jungsoon, Kim, Ji-Hyun, Chang, Changsoo, Tsai, Francis T. F., & Lee, Sukyeong. 2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix. United States. doi:10.1107/S2059798316009906.
Sung, Nuri, Lee, Jungsoon, Kim, Ji-Hyun, Chang, Changsoo, Tsai, Francis T. F., and Lee, Sukyeong. 2016. "2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix". United States. doi:10.1107/S2059798316009906.
@article{osti_1337160,
title = {2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix},
author = {Sung, Nuri and Lee, Jungsoon and Kim, Ji-Hyun and Chang, Changsoo and Tsai, Francis T. F. and Lee, Sukyeong},
abstractNote = {TRAP1 is an organelle-specific Hsp90 paralog that is essential for neoplastic growth. As a member of the Hsp90 family, TRAP1 is presumed to be a general chaperone facilitating the late-stage folding of Hsp90 client proteins in the mitochondrial matrix. Interestingly, TRAP1 cannot replace cytosolic Hsp90 in protein folding, and none of the known Hsp90 co-chaperones are found in mitochondria. Thus, the three-dimensional structure of TRAP1 must feature regulatory elements that are essential to the ATPase activity and chaperone function of TRAP1. Here, the crystal structure of a human TRAP1NMdimer is presented, featuring an intact N-domain and M-domain structure, bound to adenosine 5'-β,γ-imidotriphosphate (ADPNP). The crystal structure together with epitope-mapping results shows that the TRAP1 M-domain loop 1 contacts the neighboring subunit and forms a previously unobserved third dimer interface that mediates the specific interaction with mitochondrial Hsp70.},
doi = {10.1107/S2059798316009906},
journal = {Acta Crystallographica. Section D. Structural Biology},
number = 8,
volume = 72,
place = {United States},
year = 2016,
month = 7
}
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