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3hpg

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Revision as of 08:07, 12 December 2018

Visna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open integrase dimer-dimer interfaces

Structural highlights

3hpg is a 12 chain structure with sequence from Human and Mvv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1k6y, 2b4j, 3f9k, 3hph
Gene:	pol (MVV), DFS70, LEDGF, PSIP1, PSIP2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PSIP1_HUMAN] Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4.

Function

[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. [PSIP1_HUMAN] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.^[1]

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 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^[2]

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

References

↑ Chylack LT Jr, Fu L, Mancini R, Martin-Rehrmann MD, Saunders AJ, Konopka G, Tian D, Hedley-Whyte ET, Folkerth RD, Goldstein LE. Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain. Exp Eye Res. 2004 Dec;79(6):941-8. PMID:15642333 doi:S0014-4835(04)00250-7
↑ Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P. Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog. 2009 Jul;5(7):e1000515. Epub 2009 Jul 17. PMID:19609359 doi:10.1371/journal.ppat.1000515

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3hpg"

@@ 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]] 3.28&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1k6y|1k6y]], [[2b4j|2b4j]], [[3f9k|3f9k]], [[3hph|3hph]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36374 MVV]), DFS70, LEDGF, PSIP1, PSIP2 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hpg OCA], [http://pdbe.org/3hpg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hpg RCSB], [http://www.ebi.ac.uk/pdbsum/3hpg PDBsum]</span></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=3hpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hpg OCA], [http://pdbe.org/3hpg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hpg RCSB], [http://www.ebi.ac.uk/pdbsum/3hpg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hpg ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hp/3hpg_consurf.spt"</scriptWhenChecked>
+    <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>
@@ Line 63: / Line 64: @@
 [[Category: Viral protein]]
 [[Category: Virion]]
+[[Category: Zinc]]
 [[Category: Zinc binding]]

3hpg

From Proteopedia

Revision as of 08:07, 12 December 2018

Visna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open integrase dimer-dimer interfaces

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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