8HL7

Crystal structure of p97 N/D1 in complex with a valosin-containing protein methyltransferase

Summary for 8HL7

• Entry DOI: 10.2210/pdb8hl7/pdb
• Descriptor: Protein N-lysine methyltransferase METTL21D, Transitional endoplasmic reticulum ATPase, S-ADENOSYL-L-HOMOCYSTEINE, ... (9 entities in total)
• Functional Keywords: vcpkmt, methyltransferase, trimethylated lysine, aspl, aspscr1, ubxd9, tug, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 73769.30

Authors

Kang, W.,Yang, J.K. (deposition date: 2022-11-29, release date: 2023-07-12, Last modification date: 2023-08-02)

Primary citation

Nguyen, T.Q.,Koh, S.,Kwon, J.,Jang, S.,Kang, W.,Yang, J.K.
Structural basis for recognition and methylation of p97 by METTL21D, a valosin-containing protein lysine methyltransferase.
Iscience, 26:107222-107222, 2023

PubMed Abstract: p97 is a human AAA+ (ATPase associated with diverse cellular activities, also known as valosin-containing protein [VCP]) ATPase, which is involved in diverse cellular processes such as membrane fusion and proteolysis. Lysine-specific methyltransferase of p97 (METTL21D) was identified as a class I methyltransferase that catalyzes the trimethylation of Lys315 of p97, a so-called VCP lysine methyltransferase (VCPKMT). Interestingly, VCPKMT disassembles a single hexamer ring consisting of p97-D1 domain and methylates Lys315 residue. Herein, the structures of S-adenosyl-L-methionine-bound VCPKMT and S-adenosyl-L-homocysteine-bound VCPKMT in complex with p97 N/D1 (N21-Q458) were reported at a resolution of 1.8 Å and 2.8 Å, respectively. The structures revealed the molecular details for the recognition and methylation of monomeric p97 by VCPKMT. Using biochemical analysis, we also investigated whether the methylation of full-length p97 could be sufficiently enhanced through cooperation between VCPKMT and the C terminus of alveolar soft part sarcoma locus (ASPL). Our study provides the groundwork for future structural and mechanistic studies of p97 and inhibitors.

PubMed: 37456834
DOI: 10.1016/j.isci.2023.107222

Experimental method

X-RAY DIFFRACTION (2.8 Å)