4KO8

Structure of p97 N-D1 R155H mutant in complex with ATPgS

4KO8 の概要

• エントリーDOI: 10.2210/pdb4ko8/pdb
• 関連するPDBエントリー: 4KLN 4KOD
• 分子名称: Transitional endoplasmic reticulum ATPase, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: atpase, transport protein, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol: P55072
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 110219.64

構造登録者

Xia, D.,Tang, W.K. (登録日: 2013-05-11, 公開日: 2013-11-13, 最終更新日: 2024-02-28)

主引用文献

Tang, W.K.,Xia, D.
Altered Intersubunit Communication Is the Molecular Basis for Functional Defects of Pathogenic p97 Mutants.
J.Biol.Chem., 288:36624-36635, 2013

PubMed Abstract: The human AAA ATPase p97 is a molecular chaperone essential in cellular proteostasis. Single amino acid substitutions in p97 have been linked to a clinical multiple-disorder condition known as inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia. How the mutations affect the molecular mechanism that governs the function of p97 remains unclear. Here, we show that within the hexameric ring of a mutant p97, D1 domains fail to regulate their respective nucleotide-binding states, as evidenced by the lower amount of prebound ADP, weaker ADP binding affinity, full occupancy of adenosine-5'-O-(3-thiotriphosphate) binding, and elevated overall ATPase activity, indicating a loss of communication among subunits. Defective communication between subunits is further illustrated by altered conformation in the side chain of residue Phe-360 that probes into the nucleotide-binding pocket from a neighboring subunit. Consequently, conformations of N domains in a hexameric ring of a mutant p97 become uncoordinated, thus impacting its ability to process substrate.

PubMed: 24196964
DOI: 10.1074/jbc.M113.488924

実験手法

X-RAY DIFFRACTION (1.98 Å)