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2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix
Author(s) -
Sung Nuri,
Lee Jungsoon,
Kim Ji-Hyun,
Chang Changsoo,
Tsai Francis T. F.,
Lee Sukyeong
Publication year - 2016
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798316009906
Subject(s) - hsp90 , chaperone (clinical) , protein subunit , mitochondrial matrix , dimer , organelle , protein folding , chemistry , mitochondrion , microbiology and biotechnology , crystallography , biology , cytosol , biochemistry , heat shock protein , enzyme , medicine , organic chemistry , pathology , gene
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 NM dimer 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.