4KBO

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

4KBO の概要

• エントリーDOI: 10.2210/pdb4kbo/pdb
• 関連するPDBエントリー: 2E88 3ATU
• 分子名称: Stress-70 protein, mitochondrial, SODIUM ION (3 entities in total)
• 機能のキーワード: atpase, atp binding, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion: P38646
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41439.05

構造登録者

Amick, J.,Page, R.C.,Nix, J.C.,Misra, S. (登録日: 2013-04-23, 公開日: 2014-04-02, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)