Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

4KOD

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

Summary for 4KOD
Entry DOI10.2210/pdb4kod/pdb
Related4KLN 4KO8
DescriptorTransitional endoplasmic reticulum ATPase, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
Functional Keywordsaaa atpase, transport protein, hydrolase
Biological sourceHomo sapiens (human)
Cellular locationCytoplasm, cytosol: P55072
Total number of polymer chains12
Total formula weight659873.60
Authors
Xia, D.,Tang, W.K. (deposition date: 2013-05-11, release date: 2013-11-13, Last modification date: 2024-02-28)
Primary citationTang, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.96 Å)
Structure validation

229183

数据于2024-12-18公开中

PDB statisticsPDBj update infoContact PDBjnumon