7e58: Difference between revisions
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==interferon-inducible anti-viral protein 2== | ==interferon-inducible anti-viral protein 2== | ||
<StructureSection load='7e58' size='340' side='right'caption='[[7e58]]' scene=''> | <StructureSection load='7e58' size='340' side='right'caption='[[7e58]], [[Resolution|resolution]] 2.60Å' 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=7E58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E58 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7e58]] is a 2 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=7E58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E58 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=7e58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e58 OCA], [https://pdbe.org/7e58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e58 RCSB], [https://www.ebi.ac.uk/pdbsum/7e58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e58 ProSAT]</span></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]] 2.6Å</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=7e58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e58 OCA], [https://pdbe.org/7e58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e58 RCSB], [https://www.ebi.ac.uk/pdbsum/7e58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e58 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/GBP2_HUMAN GBP2_HUMAN] Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:31091448). Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions, but the major reaction product is GDP (PubMed:8706832). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (By similarity). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (By similarity). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (By similarity). Confers protection to the protozoan pathogen Toxoplasma gondii (By similarity). Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity, such as HIV-1, Zika and influenza A viruses, by inhibiting FURIN-mediated maturation of viral envelope proteins (PubMed:31091448).[UniProtKB:Q9Z0E6]<ref>PMID:31091448</ref> <ref>PMID:8706832</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP51-486), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP51-486 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function. | |||
Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.,Cui W, Braun E, Wang W, Tang J, Zheng Y, Slater B, Li N, Chen C, Liu Q, Wang B, Li X, Duan Y, Xiao Y, Ti R, Hotter D, Ji X, Zhang L, Cui J, Xiong Y, Sauter D, Wang Z, Kirchhoff F, Yang H Proc Natl Acad Sci U S A. 2021 Apr 13;118(15). pii: 2022269118. doi:, 10.1073/pnas.2022269118. PMID:33876762<ref>PMID:33876762</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7e58" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chen C]] | [[Category: Chen C]] | ||