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2lm0

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Revision as of 11:07, 15 February 2023

Solution structure of the AF4-AF9 complex

Structural highlights

2lm0 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AFF1_HUMAN Precursor B-cell acute lymphoblastic leukemia. A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with KMT2A/MLL1. The result is a rogue activator protein.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

AFF1_HUMAN 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

Mixed lineage leukemia (MLL) fusion proteins cause oncogenic transformation of hematopoietic cells by constitutive recruitment of elongation factors to HOX promoters, resulting in overexpression of target genes. The structural basis of transactivation by MLL fusion partners remains undetermined. We show that the ANC1 homology domain (AHD) of AF9, one of the most common MLL translocation partners, is intrinsically disordered and recruits multiple transcription factors through coupled folding and binding. We determined the structure of the AF9 AHD in complex with the elongation factor AF4 and show that aliphatic residues, which are conserved in each of the AF9 binding partners, form an integral part of the hydrophobic core of the complex. Nuclear magnetic resonance relaxation measurements show that AF9 retains significant dynamic behavior which may facilitate exchange between disordered partners. We propose that AF9 functions as a signaling hub that regulates transcription through dynamic recruitment of cofactors in normal hematopoiesis and in acute leukemia.

Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding.,Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH Structure. 2012 Dec 19. pii: S0969-2126(12)00426-1. doi:, 10.1016/j.str.2012.11.011. PMID:23260655^[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
↑ Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH. Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding. Structure. 2012 Dec 19. pii: S0969-2126(12)00426-1. doi:, 10.1016/j.str.2012.11.011. PMID:23260655 doi:http://dx.doi.org/10.1016/j.str.2012.11.011

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lm0"

@@ Line 1: / Line 1: @@
 ==Solution structure of the AF4-AF9 complex==
-<StructureSection load='2lm0' size='340' side='right'caption='[[2lm0]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='2lm0' size='340' side='right'caption='[[2lm0]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2lm0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LM0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2lm0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LM0 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFF1, AF4, FEL, MLLT2, PBM1, MLLT3, AF9, YEATS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lm0 OCA], [https://pdbe.org/2lm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lm0 RCSB], [https://www.ebi.ac.uk/pdbsum/2lm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lm0 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lm0 OCA], [https://pdbe.org/2lm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lm0 RCSB], [https://www.ebi.ac.uk/pdbsum/2lm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lm0 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/AFF1_HUMAN AFF1_HUMAN]] Precursor B-cell acute lymphoblastic leukemia. A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with KMT2A/MLL1. The result is a rogue activator protein.
+[https://www.uniprot.org/uniprot/AFF1_HUMAN AFF1_HUMAN] Precursor B-cell acute lymphoblastic leukemia. A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with KMT2A/MLL1. The result is a rogue activator protein.[https://www.uniprot.org/uniprot/AF9_HUMAN 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 ==
+[https://www.uniprot.org/uniprot/AFF1_HUMAN AFF1_HUMAN] [https://www.uniprot.org/uniprot/AF9_HUMAN 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.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bushweller, J H]]
+[[Category: Bushweller JH]]
-[[Category: Cierpicki, T]]
+[[Category: Cierpicki T]]
-[[Category: Johnson, S A]]
+[[Category: Johnson SA]]
-[[Category: Kuntimaddi, A]]
+[[Category: Kuntimaddi A]]
-[[Category: Leach, B I]]
+[[Category: Leach BI]]
-[[Category: Schmidt, C R]]
+[[Category: Schmidt CR]]
-[[Category: Intrinsically disordered]]
-[[Category: Nuclear protein]]

2lm0

From Proteopedia

Revision as of 11:07, 15 February 2023

Solution structure of the AF4-AF9 complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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