4tmp: Difference between revisions

Revision as of 06:16, 17 April 2019

Crystal structure of AF9 YEATS bound to H3K9ac peptide

Structural highlights

4tmp 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.
Ligands:	EDO
NonStd Res:	ALY
Gene:	MLLT3, AF9, YEATS3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[AF9_HUMAN] A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein.

Function

[AF9_HUMAN] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.^[1] ^[2]

Publication Abstract from PubMed

The recognition of modified histones by "reader" proteins constitutes a key mechanism regulating gene expression in the chromatin context. Compared with the great variety of readers for histone methylation, few protein modules that recognize histone acetylation are known. Here, we show that the AF9 YEATS domain binds strongly to histone H3K9 acetylation and, to a lesser extent, H3K27 and H3K18 acetylation. Crystal structural studies revealed that AF9 YEATS adopts an eight-stranded immunoglobin fold and utilizes a serine-lined aromatic "sandwiching" cage for acetyllysine readout, representing a novel recognition mechanism that is distinct from that of known acetyllysine readers. ChIP-seq experiments revealed a strong colocalization of AF9 and H3K9 acetylation genome-wide, which is important for the chromatin recruitment of the H3K79 methyltransferase DOT1L. Together, our studies identified the evolutionarily conserved YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.

AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation.,Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SY, Li W, Li H, Shi X Cell. 2014 Oct 23;159(3):558-71. doi: 10.1016/j.cell.2014.09.049. PMID:25417107^[3]

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

References

↑ Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010 Feb 12;37(3):429-37. doi: 10.1016/j.molcel.2010.01.026. PMID:20159561 doi:10.1016/j.molcel.2010.01.026
↑ He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, Krogan NJ, Alber T, Zhou Q. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010 May 14;38(3):428-38. doi: 10.1016/j.molcel.2010.04.013. PMID:20471948 doi:10.1016/j.molcel.2010.04.013
↑ Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SY, Li W, Li H, Shi X. AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation. Cell. 2014 Oct 23;159(3):558-71. doi: 10.1016/j.cell.2014.09.049. PMID:25417107 doi:https://dx.doi.org/10.1016/j.cell.2014.09.049

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010 Feb 12;37(3):429-37. doi: 10.1016/j.molcel.2010.01.026. PMID:20159561 doi:10.1016/j.molcel.2010.01.026

[2] He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, Krogan NJ, Alber T, Zhou Q. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010 May 14;38(3):428-38. doi: 10.1016/j.molcel.2010.04.013. PMID:20471948 doi:10.1016/j.molcel.2010.04.013

[3] Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SY, Li W, Li H, Shi X. AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation. Cell. 2014 Oct 23;159(3):558-71. doi: 10.1016/j.cell.2014.09.049. PMID:25417107 doi:https://dx.doi.org/10.1016/j.cell.2014.09.049

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[2]

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@@ Line 1: / Line 1: @@
 ==Crystal structure of AF9 YEATS bound to H3K9ac peptide==
-<StructureSection load='4tmp' size='340' side='right' caption='[[4tmp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='4tmp' size='340' side='right'caption='[[4tmp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4tmp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TMP FirstGlance]. <br>
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Li, H]]
 [[Category: Li, Y]]

4tmp: Difference between revisions

Revision as of 06:16, 17 April 2019

Crystal structure of AF9 YEATS bound to H3K9ac peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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