6ago | pdb_00006ago

Crystal structure of MRG15-ASH1L Histone methyltransferase complex

spinqualitylabelsall models 6ago, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ago is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SAM, ZN Activity: Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ASH1L_HUMAN] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me). Publication Abstract from PubMed Human ASH1L is the catalytic subunit of the conserved histone methyltransferase (HMTase) complex AMC that dimethylates lysine 36 in histone H3 (H3K36me2) to promote gene transcription in mammals and flies. Unlike AMC, ASH1L alone shows poor catalytic activity, because access to its substrate binding pocket is blocked by an autoinhibitory loop (AI loop) from the postSET domain. We report the crystal structure of the minimal catalytic active AMC complex containing ASH1L and its partner subunit MRG15. The structure reveals how binding of the MRG domain of MRG15 to a conserved FxLP motif in ASH1L results in the displacement of the AI loop to permit substrates to access the catalytic pocket of the ASH1L SET domain. Together, ASH1L activation by MRG15 therefore represents a delicate regulatory mechanism for how a cofactor activates an SET domain HMTase by releasing autoinhibition. Structural Basis of MRG15-Mediated Activation of the ASH1L Histone Methyltransferase by Releasing an Autoinhibitory Loop.,Lee Y, Yoon E, Cho S, Schmahling S, Muller J, Song JJ Structure. 2019 Feb 9. pii: S0969-2126(19)30016-4. doi:, 10.1016/j.str.2019.01.016. PMID:30827841 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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