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==Higher-order assembly of multiple MMTV strand transfer complex intasomes== | ==Higher-order assembly of multiple MMTV strand transfer complex intasomes== | ||
<StructureSection load='7ut1' size='340' side='right'caption='[[7ut1]]' scene=''> | <StructureSection load='7ut1' size='340' side='right'caption='[[7ut1]], [[Resolution|resolution]] 3.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UT1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ut1]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Mouse_mammary_tumor_virus Mouse mammary tumor virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UT1 FirstGlance]. <br> | ||
</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=7ut1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ut1 OCA], [https://pdbe.org/7ut1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ut1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ut1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ut1 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7ut1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ut1 OCA], [https://pdbe.org/7ut1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ut1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ut1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ut1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Integration into host target DNA (tDNA), a hallmark of retroviral replication, is mediated by the intasome, a multimer of integrase (IN) assembled on viral DNA (vDNA) ends. To ascertain aspects of tDNA recognition during integration, we have solved the 3.5 A resolution cryo-EM structure of the mouse mammary tumor virus (MMTV) strand transfer complex (STC) intasome. The tDNA adopts an A-like conformation in the region encompassing the sites of vDNA joining, which exposes the sugar-phosphate backbone for IN-mediated strand transfer. Examination of existing retroviral STC structures revealed conservation of A-form tDNA in the analogous regions of these complexes. Furthermore, analyses of sequence preferences in genomic integration sites selectively targeted by six different retroviruses highlighted consistent propensity for A-philic sequences at the sites of vDNA joining. Our structure additionally revealed several novel MMTV IN-DNA interactions, as well as contacts seen in prior STC structures, including conserved Pro125 and Tyr149 residues interacting with tDNA. In infected cells, Pro125 substitutions impacted the global pattern of MMTV integration without significantly altering local base sequence preferences at vDNA insertion sites. Collectively, these data advance our understanding of retroviral intasome structure and function, as well as factors that influence patterns of vDNA integration in genomic DNA. | |||
B-to-A transition in target DNA during retroviral integration.,Jozwik IK, Li W, Zhang DW, Wong D, Grawenhoff J, Ballandras-Colas A, Aiyer S, Cherepanov P, Engelman AN, Lyumkis D Nucleic Acids Res. 2022 Aug 26;50(15):8898-8918. doi: 10.1093/nar/gkac644. PMID:35947647<ref>PMID:35947647</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ut1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Mouse mammary tumor virus]] | |||
[[Category: Jozwik I]] | [[Category: Jozwik I]] | ||
[[Category: Lyumkis D]] | [[Category: Lyumkis D]] | ||
Latest revision as of 08:14, 12 June 2024
Higher-order assembly of multiple MMTV strand transfer complex intasomesHigher-order assembly of multiple MMTV strand transfer complex intasomes
Structural highlights
Publication Abstract from PubMedIntegration into host target DNA (tDNA), a hallmark of retroviral replication, is mediated by the intasome, a multimer of integrase (IN) assembled on viral DNA (vDNA) ends. To ascertain aspects of tDNA recognition during integration, we have solved the 3.5 A resolution cryo-EM structure of the mouse mammary tumor virus (MMTV) strand transfer complex (STC) intasome. The tDNA adopts an A-like conformation in the region encompassing the sites of vDNA joining, which exposes the sugar-phosphate backbone for IN-mediated strand transfer. Examination of existing retroviral STC structures revealed conservation of A-form tDNA in the analogous regions of these complexes. Furthermore, analyses of sequence preferences in genomic integration sites selectively targeted by six different retroviruses highlighted consistent propensity for A-philic sequences at the sites of vDNA joining. Our structure additionally revealed several novel MMTV IN-DNA interactions, as well as contacts seen in prior STC structures, including conserved Pro125 and Tyr149 residues interacting with tDNA. In infected cells, Pro125 substitutions impacted the global pattern of MMTV integration without significantly altering local base sequence preferences at vDNA insertion sites. Collectively, these data advance our understanding of retroviral intasome structure and function, as well as factors that influence patterns of vDNA integration in genomic DNA. B-to-A transition in target DNA during retroviral integration.,Jozwik IK, Li W, Zhang DW, Wong D, Grawenhoff J, Ballandras-Colas A, Aiyer S, Cherepanov P, Engelman AN, Lyumkis D Nucleic Acids Res. 2022 Aug 26;50(15):8898-8918. doi: 10.1093/nar/gkac644. PMID:35947647[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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