8szk: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
The | ==The cryo-EM structure of PPP2R5A/HIV-1 Vif/CBFb/EloB/EloC complex== | ||
<StructureSection load='8szk' size='340' side='right'caption='[[8szk]], [[Resolution|resolution]] 3.58Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8szk]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(NEW_YORK-5_ISOLATE) Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SZK FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.58Å</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=8szk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8szk OCA], [https://pdbe.org/8szk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8szk RCSB], [https://www.ebi.ac.uk/pdbsum/8szk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8szk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/2A5A_HUMAN 2A5A_HUMAN] The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFbeta to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the regulatory subunits PPP2R5(A-E) of cellular protein phosphatase 2A to induce G2/M cell cycle arrest. As PPP2R5 proteins bear no functional or structural resemblance to A3s, it is unclear how Vif can recognize different sets of proteins. Here we report the cryogenic-electron microscopy structure of PPP2R5A in complex with HIV-1 Vif-CBFbeta-elongin B-elongin C at 3.58 A resolution. The structure shows PPP2R5A binds across the Vif molecule, with biochemical and cellular studies confirming a distinct Vif-PPP2R5A interface that partially overlaps with those for A3s. Vif also blocks a canonical PPP2R5A substrate-binding site, indicating that it suppresses the phosphatase activities through both degradation-dependent and degradation-independent mechanisms. Our work identifies critical Vif motifs regulating the recognition of diverse A3 and PPP2R5A substrates, whereby disruption of these host-virus protein interactions could serve as potential targets for HIV-1 therapeutics. | |||
Structural insights into PPP2R5A degradation by HIV-1 Vif.,Hu Y, Delviks-Frankenberry KA, Wu C, Arizaga F, Pathak VK, Xiong Y Nat Struct Mol Biol. 2024 May 24. doi: 10.1038/s41594-024-01314-6. PMID:38789685<ref>PMID:38789685</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8szk" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Hu Y]] | |||
[[Category: Xiong Y]] | |||
Latest revision as of 08:19, 5 June 2024
The cryo-EM structure of PPP2R5A/HIV-1 Vif/CBFb/EloB/EloC complexThe cryo-EM structure of PPP2R5A/HIV-1 Vif/CBFb/EloB/EloC complex
Structural highlights
Function2A5A_HUMAN The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Publication Abstract from PubMedHIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFbeta to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the regulatory subunits PPP2R5(A-E) of cellular protein phosphatase 2A to induce G2/M cell cycle arrest. As PPP2R5 proteins bear no functional or structural resemblance to A3s, it is unclear how Vif can recognize different sets of proteins. Here we report the cryogenic-electron microscopy structure of PPP2R5A in complex with HIV-1 Vif-CBFbeta-elongin B-elongin C at 3.58 A resolution. The structure shows PPP2R5A binds across the Vif molecule, with biochemical and cellular studies confirming a distinct Vif-PPP2R5A interface that partially overlaps with those for A3s. Vif also blocks a canonical PPP2R5A substrate-binding site, indicating that it suppresses the phosphatase activities through both degradation-dependent and degradation-independent mechanisms. Our work identifies critical Vif motifs regulating the recognition of diverse A3 and PPP2R5A substrates, whereby disruption of these host-virus protein interactions could serve as potential targets for HIV-1 therapeutics. Structural insights into PPP2R5A degradation by HIV-1 Vif.,Hu Y, Delviks-Frankenberry KA, Wu C, Arizaga F, Pathak VK, Xiong Y Nat Struct Mol Biol. 2024 May 24. doi: 10.1038/s41594-024-01314-6. PMID:38789685[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||