3hpg: Difference between revisions
No edit summary |
No edit summary |
||
| (10 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Visna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open integrase dimer-dimer interfaces== | |||
<StructureSection load='3hpg' size='340' side='right'caption='[[3hpg]], [[Resolution|resolution]] 3.28Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3hpg]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Visna/maedi_virus_EV1_KV1772 Visna/maedi virus EV1 KV1772]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HPG FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.28Å</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=3hpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hpg OCA], [https://pdbe.org/3hpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hpg RCSB], [https://www.ebi.ac.uk/pdbsum/3hpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hpg ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/POL_VILVK POL_VILVK] During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the host chromosome by the viral integrase enzyme. RNase H activity is associated with the reverse transcriptase. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hp/3hpg_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hpg ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Experimental evidence suggests that a tetramer of integrase (IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor. | |||
Structural basis for functional tetramerization of lentiviral integrase.,Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P PLoS Pathog. 2009 Jul;5(7):e1000515. Epub 2009 Jul 17. PMID:19609359<ref>PMID:19609359</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3hpg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Visna/maedi virus EV1 KV1772]] | |||
[[Category: Cherepanov P]] | |||
[[Category: Hare S]] | |||
[[Category: Labeja A]] | |||
Latest revision as of 18:52, 1 November 2023
Visna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open integrase dimer-dimer interfacesVisna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open integrase dimer-dimer interfaces
Structural highlights
FunctionPOL_VILVK During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the host chromosome by the viral integrase enzyme. RNase H activity is associated with the reverse transcriptase. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedExperimental evidence suggests that a tetramer of integrase (IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor. Structural basis for functional tetramerization of lentiviral integrase.,Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P PLoS Pathog. 2009 Jul;5(7):e1000515. Epub 2009 Jul 17. PMID:19609359[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||