5F3K

X-Ray Crystallographic Structure of hTrap1 N-terminal Domain-apo

Summary for 5F3K

• Entry DOI: 10.2210/pdb5f3k/pdb
• Related: 5F5R
• Descriptor: Heat shock protein 75 kDa, mitochondrial (2 entities in total)
• Functional Keywords: trap1, hsp90, chaperone, apo
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 52092.29

Authors

Sung, N.,Lee, J.,Kim, J.,Chang, C.,Joachimiak, A.,Lee, S.,Tsai, F.T.F. (deposition date: 2015-12-02, release date: 2016-03-02, Last modification date: 2023-09-27)

Primary citation

Sung, N.,Lee, J.,Kim, J.H.,Chang, C.,Joachimiak, A.,Lee, S.,Tsai, F.T.
Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate.
Proc.Natl.Acad.Sci.USA, 113:2952-2957, 2016

PubMed Abstract: Heat-shock protein of 90 kDa (Hsp90) is an essential molecular chaperone that adopts different 3D structures associated with distinct nucleotide states: a wide-open, V-shaped dimer in the apo state and a twisted, N-terminally closed dimer with ATP. Although the N domain is known to mediate ATP binding, how Hsp90 senses the bound nucleotide and facilitates dimer closure remains unclear. Here we present atomic structures of human mitochondrial Hsp90N (TRAP1N) and a composite model of intact TRAP1 revealing a previously unobserved coiled-coil dimer conformation that may precede dimer closure and is conserved in intact TRAP1 in solution. Our structure suggests that TRAP1 normally exists in an autoinhibited state with the ATP lid bound to the nucleotide-binding pocket. ATP binding displaces the ATP lid that signals the cis-bound ATP status to the neighboring subunit in a highly cooperative manner compatible with the coiled-coil intermediate state. We propose that TRAP1 is a ligand-activated molecular chaperone, which couples ATP binding to dramatic changes in local structure required for protein folding.

PubMed: 26929380
DOI: 10.1073/pnas.1516167113

Experimental method

X-RAY DIFFRACTION (1.82 Å)