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5jw9

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Revision as of 11:42, 17 June 2020

The Crystal Structure of ELL2 Oclludin Domain and AFF4 peptide

Structural highlights

5jw9 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	AFF4, AF5Q31, MCEF, HSPC092 (HUMAN), ELL2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[AFF4_HUMAN] Note=A chromosomal aberration involving AFF4 is found in acute lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that forms a MLL-AFF4 fusion protein.

Function

[AFF4_HUMAN] Key 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. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression.^[1] ^[2] ^[3] [ELL2_HUMAN] Elongation factor 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. Plays a role in immunoglobulin secretion in plasma cells: directs efficient alternative mRNA processing, influencing both proximal poly(A) site choice and exon skipping, as well as immunoglobulin heavy chain (IgH) alternative processing. Probably acts by regulating histone modifications accompanying transition from membrane-specific to secretory IgH mRNA expression.^[4] ^[5] ^[6]

Publication Abstract from PubMed

The intrinsically disordered scaffold proteins AFF1/4 and the transcription elongation factors ELL1/2 are core components of the super elongation complex required for HIV-1 proviral transcription. Here we report the 2.0-A resolution crystal structure of the human ELL2 C-terminal domain bound to its 50-residue binding site on AFF4, the ELLBow. The ELL2 domain has the same arch-shaped fold as the tight junction protein occludin. The ELLBow consists of an N-terminal helix followed by an extended hairpin that we refer to as the elbow joint, and occupies most of the concave surface of ELL2. This surface is important for the ability of ELL2 to promote HIV-1 Tat-mediated proviral transcription. The AFF4-ELL2 interface is imperfectly packed, leaving a cavity suggestive of a potential binding site for transcription-promoting small molecules.

Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription.,Qi S, Li Z, Schulze-Gahmen U, Stjepanovic G, Zhou Q, Hurley JH Nat Commun. 2017 Jan 30;8:14076. doi: 10.1038/ncomms14076. PMID:28134250^[7]

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

References

↑ 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
↑ 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
↑ Chou S, Upton H, Bao K, Schulze-Gahmen U, Samelson AJ, He N, Nowak A, Lu H, Krogan NJ, Zhou Q, Alber T. HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):E123-31. doi:, 10.1073/pnas.1216971110. Epub 2012 Dec 18. PMID:23251033 doi:10.1073/pnas.1216971110
↑ 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
↑ 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
↑ Chou S, Upton H, Bao K, Schulze-Gahmen U, Samelson AJ, He N, Nowak A, Lu H, Krogan NJ, Zhou Q, Alber T. HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):E123-31. doi:, 10.1073/pnas.1216971110. Epub 2012 Dec 18. PMID:23251033 doi:10.1073/pnas.1216971110
↑ Qi S, Li Z, Schulze-Gahmen U, Stjepanovic G, Zhou Q, Hurley JH. Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription. Nat Commun. 2017 Jan 30;8:14076. doi: 10.1038/ncomms14076. PMID:28134250 doi:http://dx.doi.org/10.1038/ncomms14076

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jw9"

@@ Line 1: / Line 1: @@
 ==The Crystal Structure of ELL2 Oclludin Domain and AFF4 peptide==
-<StructureSection load='5jw9' size='340' side='right' caption='[[5jw9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5jw9' size='340' side='right'caption='[[5jw9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jw9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JW9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jw9]] is a 2 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=5JW9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JW9 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jw9 OCA], [http://pdbe.org/5jw9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jw9 RCSB], [http://www.ebi.ac.uk/pdbsum/5jw9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jw9 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFF4, AF5Q31, MCEF, HSPC092 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ELL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jw9 OCA], [http://pdbe.org/5jw9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jw9 RCSB], [http://www.ebi.ac.uk/pdbsum/5jw9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jw9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5jw9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Elongation factor 3D structures|Elongation factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hurley, J H]]
 [[Category: Qi, S]]

5jw9

From Proteopedia

Revision as of 11:42, 17 June 2020

The Crystal Structure of ELL2 Oclludin Domain and AFF4 peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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