Structural highlights
6ago is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Gene: | ASH1L, KIAA1420, KMT2H (HUMAN), MORF4L1, MRG15, FWP006, HSPC008, HSPC061, PP368 (HUMAN) |
| 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).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ An S, Yeo KJ, Jeon YH, Song JJ. Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J Biol Chem. 2011 Mar 11;286(10):8369-74. Epub 2011 Jan 14. PMID:21239497 doi:10.1074/jbc.M110.203380
- ↑ Lee Y, Yoon E, Cho S, Schmahling S, Muller J, Song JJ. Structural Basis of MRG15-Mediated Activation of the ASH1L Histone Methyltransferase by Releasing an Autoinhibitory Loop. Structure. 2019 Feb 9. pii: S0969-2126(19)30016-4. doi:, 10.1016/j.str.2019.01.016. PMID:30827841 doi:http://dx.doi.org/10.1016/j.str.2019.01.016
