8hl6

Crystal structure of human valosin-containing protein methyltransferase

spinqualitylabelsall models 8hl6, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hl6 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: SAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MT21D_HUMAN Protein-lysine N-methyltransferase that specifically trimethylates 'Lys-315' of VCP/p97. Publication Abstract from PubMed 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 A and 2.8 A, 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. Structural basis for recognition and methylation of p97 by METTL21D, a valosin-containing protein lysine methyltransferase.,Nguyen TQ, Koh S, Kwon J, Jang S, Kang W, Yang JK iScience. 2023 Jun 26;26(7):107222. doi: 10.1016/j.isci.2023.107222. eCollection , 2023 Jul 21. PMID:37456834 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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