5DYG

Structure of p97 N-D1 L198W mutant in complex with ADP

Summary for 5DYG

• Entry DOI: 10.2210/pdb5dyg/pdb
• Related: 5DYI
• Descriptor: Transitional endoplasmic reticulum ATPase, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: vcp, aaa atpase, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytosol: P55072
• Total number of polymer chains: 1
• Total formula weight: 52816.08

Authors

Tang, W.K.,Xia, D. (deposition date: 2015-09-24, release date: 2016-02-10, Last modification date: 2024-03-06)

Primary citation

Tang, W.K.,Xia, D.
Role of the D1-D2 Linker of Human VCP/p97 in the Asymmetry and ATPase Activity of the D1-domain.
Sci Rep, 6:20037-20037, 2016

PubMed Abstract: Human AAA(+) protein p97 consists of an N-domain and two tandem ATPase domains D1 and D2, which are connected by the N-D1 and the D1-D2 linkers. Inclusion of the D1-D2 linker, a 22-amino acid peptide, at the end of p97 N-D1 truncate has been shown to activate ATP hydrolysis of its D1-domain, although the mechanism of activation remains unclear. Here, we identify the N-terminal half of this linker, highly conserved from human to fungi, is essential for the ATPase activation. By analyzing available crystal structures, we observed that the D1-D2 linker is capable of inducing asymmetry in subunit association into a p97 hexamer. This observation is reinforced by two new crystal structures, determined in the present work. The effect of D1-D2 linker on the ATPase activity of the D1-domain is correlated to the side-chain conformation of residue R359, a trans-acting arginine-finger residue essential for ATP hydrolysis of the D1-domain. The activation in D1-domain ATPase activity by breaking perfect six-fold symmetry implies functional importance of asymmetric association of p97 subunits, the extent of which can be determined quantitatively by the metric Asymmetric Index.

PubMed: 26818443
DOI: 10.1038/srep20037

Experimental method

X-RAY DIFFRACTION (2.2 Å)