6rv6: Difference between revisions

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 <StructureSection load='6rv6' size='340' side='right'caption='[[6rv6]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rv6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RV6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RV6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rv6]] 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=6RV6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RV6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 3.507&#8491;</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=6rv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rv6 OCA], [http://pdbe.org/6rv6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rv6 RCSB], [http://www.ebi.ac.uk/pdbsum/6rv6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rv6 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6rv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rv6 OCA], [https://pdbe.org/6rv6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rv6 RCSB], [https://www.ebi.ac.uk/pdbsum/6rv6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rv6 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/PROP_HUMAN PROP_HUMAN]] Defects in CFP are the cause of properdin deficiency (PFD) [MIM:[http://omim.org/entry/312060 312060]]. PFD results in higher susceptibility to bacterial infections; especially to meningococcal infections. Three phenotypes have been reported: complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin (type III).<ref>PMID:8871668</ref> <ref>PMID:9710744</ref> <ref>PMID:10909851</ref>
-== Function ==
-[[http://www.uniprot.org/uniprot/PROP_HUMAN PROP_HUMAN]] A positive regulator of the alternate pathway of complement. It binds to and stabilizes the C3- and C5-convertase enzyme complexes.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-The 54 kDa protein properdin, also known as factor P (FP), plays a major role in the complement system through the stabilization of the alternative pathway convertases. FP circulates in the blood as cyclic dimers, trimers and tetramers, and this heterogeneity challenges detailed structural insight into the mechanism of convertase stabilization by FP. Here, the generation of an intact FP monomer and a variant monomer with the third thrombospondin repeat liberated is described. Both FP monomers were excised from recombinant full-length FP containing internal cleavage sites for TEV protease. These FP monomers could be crystallized, and complete data sets extending to 2.8 A resolution for the intact FP monomer and to 3.5 A resolution for the truncated variant were collected. The principle of specific monomer excision and domain removal by the insertion of a protease cleavage site may be broadly applicable to structural studies of oligomeric, flexible and modular proteins.
+Properdin (FP) is a positive regulator of the immune system stimulating the activity of the proteolytically active C3 convertase C3bBb in the alternative pathway of the complement system. Here we present two crystal structures of FP and two structures of convertase bound FP. A structural core formed by three thrombospondin repeats (TSRs) and a TB domain harbors the convertase binding site in FP that mainly interacts with C3b. Stabilization of the interaction between the C3b C-terminus and the MIDAS bound Mg(2+) in the Bb protease by FP TSR5 is proposed to underlie FP convertase stabilization. Intermolecular contacts between FP and the convertase subunits suggested by the structure were confirmed by binding experiments. FP is shown to inhibit C3b degradation by FI due to a direct competition for a common binding site on C3b. FP oligomers are held together by two sets of intermolecular contacts, where the first is formed by the TB domain from one FP molecule and TSR4 from another. The second and largest interface is formed by TSR1 and TSR6 from the same two FP molecules. Flexibility at four hinges between thrombospondin repeats is suggested to enable the oligomeric, polydisperse, and extended architecture of FP. Our structures rationalize the effects of mutations associated with FP deficiencies and provide a structural basis for the analysis of FP function in convertases and its possible role in pattern recognition.
-Crystallization and X-ray analysis of monodisperse human properdin.,Pedersen DV, Revel M, Gadeberg TAF, Andersen GR Acta Crystallogr F Struct Biol Commun. 2019 Feb 1;75(Pt 2):0. doi:, 10.1107/S2053230X18018150. Epub 2019 Jan 23. PMID:30713161<ref>PMID:30713161</ref>
+Structural Basis for Properdin Oligomerization and Convertase Stimulation in the Human Complement System.,Pedersen DV, Gadeberg TAF, Thomas C, Wang Y, Joram N, Jensen RK, Mazarakis SMM, Revel M, El Sissy C, Petersen SV, Lindorff-Larsen K, Thiel S, Laursen NS, Fremeaux-Bacchi V, Andersen GR Front Immunol. 2019 Aug 22;10:2007. doi: 10.3389/fimmu.2019.02007. eCollection , 2019. PMID:31507604<ref>PMID:31507604</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 <div class="pdbe-citations 6rv6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Complement factor 3D structures|Complement factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Andersen, G R]]
+[[Category: Andersen GR]]
-[[Category: Pedersen, D V]]
+[[Category: Pedersen DV]]
-[[Category: Complement]]
-[[Category: Immune system]]
-[[Category: Innate immunity]]
-[[Category: Protease]]
-[[Category: Regulator]]