2.4 Å resolution crystal structure of human TRAP1NM, the Hsp90 paralog in the mitochondrial matrix

Acta Crystallogr D Struct Biol. 2016 Aug;72(Pt 8):904-11. doi: 10.1107/S2059798316009906. Epub 2016 Jul 13.


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 TRAP1NM 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.

Keywords: Hsp90 paralog; TRAP1; mitochondrial matrix; molecular chaperones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Mitochondria / chemistry
  • Mitochondria / metabolism
  • Models, Molecular
  • Protein Conformation
  • Protein Domains
  • Protein Folding
  • Protein Multimerization


  • HSP90 Heat-Shock Proteins
  • TRAP1 protein, human
  • Adenosine Triphosphate