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8h6c

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Crystal structure of human GCN5 histone acetyltransferase domain bound with malonyl-CoA

Structural highlights

8h6c is a 8 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 2.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAT2A_HUMAN Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Also acetylates non-histone proteins, such as CEBPB (PubMed:17301242). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.^[1] ^[2]

Publication Abstract from PubMed

Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less known. We here report that lysine acetyltransferase 2A (KAT2A) as an illustrative instance of HATs can selectively utilize acetyl-CoA, propionyl-CoA, butyryl-CoA, and succinyl-CoA to directly deposit 18 histone acylation hallmarks in nucleosome. By analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, succinyl-CoA, and glutaryl-CoA, we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by KAT2A. This study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes, which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells.

Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications.,Li S, Li N, He J, Zhou R, Lu Z, Tao YJ, Guo YR, Wang Y Research (Wash D C). 2023;6:0109. doi: 10.34133/research.0109. Epub 2023 Apr 4. PMID:37040526^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wiper-Bergeron N, Salem HA, Tomlinson JJ, Wu D, Hache RJ. Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPbeta by GCN5. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2703-8. Epub 2007 Feb 14. PMID:17301242 doi:http://dx.doi.org/10.1073/pnas.0607378104
↑ Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009 Mar;29(5):1176-88. doi: 10.1128/MCB.01599-08. Epub 2008 Dec, 22. PMID:19103755 doi:10.1128/MCB.01599-08
↑ Li S, Li N, He J, Zhou R, Lu Z, Tao YJ, Guo YR, Wang Y. Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications. Research (Wash D C). 2023;6:0109. PMID:37040526 doi:10.34133/research.0109