6ICV

Structure of SETD3 bound to SAH and unmodified actin

Summary for 6ICV

• Entry DOI: 10.2210/pdb6icv/pdb
• Descriptor: Histone-lysine N-methyltransferase setd3, Actin, cytoplasmic 1, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: histidine methylatransferase, protein binding, structural genomics, structural genomics consortium, sgc
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 122154.75

Authors

Guo, Q.,Liao, S.,Xu, C.,Structural Genomics Consortium (SGC) (deposition date: 2018-09-07, release date: 2019-02-27, Last modification date: 2023-11-22)

Primary citation

Guo, Q.,Liao, S.,Kwiatkowski, S.,Tomaka, W.,Yu, H.,Wu, G.,Tu, X.,Min, J.,Drozak, J.,Xu, C.
Structural insights into SETD3-mediated histidine methylation on beta-actin.
Elife, 8:-, 2019

PubMed Abstract: SETD3 is a member of the SET (Su(var)3-9, Enhancer of zeste, and Trithorax) domain protein superfamily and plays important roles in hypoxic pulmonary hypertension, muscle differentiation, and carcinogenesis. Previously, we identified SETD3 as the actin-specific methyltransferase that methylates the N3 of His73 on β-actin (Kwiatkowski et al., 2018). Here, we present two structures of -adenosyl-L-homocysteine-bound SETD3 in complex with either an unmodified β-actin peptide or its His-methylated variant. Structural analyses, supported by biochemical experiments and enzyme activity assays, indicate that the recognition and methylation of β-actin by SETD3 are highly sequence specific, and that both SETD3 and β-actin adopt pronounced conformational changes upon binding to each other. In conclusion, this study is the first to show a catalytic mechanism of SETD3-mediated histidine methylation on β-actin, which not only throws light on the protein histidine methylation phenomenon but also facilitates the design of small molecule inhibitors of SETD3.

PubMed: 30785395
DOI: 10.7554/eLife.43676

Experimental method

X-RAY DIFFRACTION (2.15 Å)