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| | <StructureSection load='6k7p' size='340' side='right'caption='[[6k7p]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6k7p' size='340' side='right'caption='[[6k7p]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6k7p]] is a 1 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=6K7P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6K7P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6k7p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K7P FirstGlance]. <br> |
| - | </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])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=6k7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k7p OCA], [http://pdbe.org/6k7p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6k7p RCSB], [http://www.ebi.ac.uk/pdbsum/6k7p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6k7p 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=6k7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k7p OCA], [https://pdbe.org/6k7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k7p RCSB], [https://www.ebi.ac.uk/pdbsum/6k7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k7p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AFF4_HUMAN 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. | + | [https://www.uniprot.org/uniprot/AFF4_HUMAN 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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AFF4_HUMAN 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.<ref>PMID:20471948</ref> <ref>PMID:20159561</ref> <ref>PMID:23251033</ref> | + | [https://www.uniprot.org/uniprot/AFF4_HUMAN 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.<ref>PMID:20471948</ref> <ref>PMID:20159561</ref> <ref>PMID:23251033</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.4 A. The alpha4, alpha5, and alpha6 of one AFF4-THD mediate the formation of a dimer and pack tightly against the equivalent part of the second molecule in the dimer of AFF-THD. Mutagenesis analysis revealed that single mutations of either Phe1014 or Tyr1096 of AFF4 to alanine impair the formation of the AFF4 dimer. In addition, transactivation assay also indicated that Phe1014 and Tyr1096 of AFF4 are critical to the transactivation activity of AFF4. Interestingly, the corresponding residues Phe1063 and Tyr1145 in AFF1 have an effect on the transactivation of HIV-1 provirus. However, such mutations of AFF1/4 have no effect on the interaction of AFF1/4 with other subunits of the SEC. Together, our data demonstrated that the dimerization of AFF1/4 is essential to transactivation of HIV-1 provirus.
| + | |
| - | | + | |
| - | Structural and functional insight into the effect of AFF4 dimerization on activation of HIV-1 proviral transcription.,Tang D, Chen C, Liao G, Liu J, Liao B, Huang Q, Chen Q, Zhao J, Jiang H, Duan J, Huang J, Wang K, Wang J, Zhou C, Chu W, Li W, Sun B, Li Z, Dai L, Fu X, Cheng W, Xue Y, Qi S Cell Discov. 2020 Feb 18;6:7. doi: 10.1038/s41421-020-0142-6. eCollection 2020. PMID:32128251<ref>PMID:32128251</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6k7p" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cheng, W]] | + | [[Category: Cheng W]] |
| - | [[Category: Duan, J]] | + | [[Category: Duan J]] |
| - | [[Category: Li, S]] | + | [[Category: Li S]] |
| - | [[Category: Qi, S]] | + | [[Category: Qi S]] |
| - | [[Category: Tang, D]] | + | [[Category: Tang D]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Xue, Y]] | + | [[Category: Xue Y]] |
| - | [[Category: Aff4]]
| + | |
| - | [[Category: Dimerizaiton]]
| + | |
| - | [[Category: Hiv-1]]
| + | |
| - | [[Category: Super elongation complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
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]
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
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