4KBO

Crystal structure of the human Mortalin (GRP75) ATPase domain in the apo form

Summary for 4KBO

• Entry DOI: 10.2210/pdb4kbo/pdb
• Related: 2E88 3ATU
• Descriptor: Stress-70 protein, mitochondrial, SODIUM ION (3 entities in total)
• Functional Keywords: atpase, atp binding, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion: P38646
• Total number of polymer chains: 1
• Total formula weight: 41439.05

Authors

Amick, J.,Page, R.C.,Nix, J.C.,Misra, S. (deposition date: 2013-04-23, release date: 2014-04-02, Last modification date: 2023-09-20)

Primary citation

Amick, J.,Schlanger, S.E.,Wachnowsky, C.,Moseng, M.A.,Emerson, C.C.,Dare, M.,Luo, W.I.,Ithychanda, S.S.,Nix, J.C.,Cowan, J.A.,Page, R.C.,Misra, S.
Crystal structure of the nucleotide-binding domain of mortalin, the mitochondrial Hsp70 chaperone.
Protein Sci., 23:833-842, 2014

PubMed Abstract: Mortalin, a member of the Hsp70-family of molecular chaperones, functions in a variety of processes including mitochondrial protein import and quality control, Fe-S cluster protein biogenesis, mitochondrial homeostasis, and regulation of p53. Mortalin is implicated in regulation of apoptosis, cell stress response, neurodegeneration, and cancer and is a target of the antitumor compound MKT-077. Like other Hsp70-family members, Mortalin consists of a nucleotide-binding domain (NBD) and a substrate-binding domain. We determined the crystal structure of the NBD of human Mortalin at 2.8 Å resolution. Although the Mortalin nucleotide-binding pocket is highly conserved relative to other Hsp70 family members, we find that its nucleotide affinity is weaker than that of Hsc70. A Parkinson's disease-associated mutation is located on the Mortalin-NBD surface and may contribute to Mortalin aggregation. We present structure-based models for how the Mortalin-NBD may interact with the nucleotide exchange factor GrpEL1, with p53, and with MKT-077. Our structure may contribute to the understanding of disease-associated Mortalin mutations and to improved Mortalin-targeting antitumor compounds.

PubMed: 24687350
DOI: 10.1002/pro.2466

Experimental method

X-RAY DIFFRACTION (2.8 Å)