8b0f: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[8b0f]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B0F FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=8b0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b0f OCA], [https://pdbe.org/8b0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b0f RCSB], [https://www.ebi.ac.uk/pdbsum/8b0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b0f ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[https://www.uniprot.org/uniprot/CO6_HUMAN CO6_HUMAN] Defects in C6 are the cause of complement component 6 deficiency (C6D) [MIM:[https://omim.org/entry/612446 612446]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.
+[https://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[https://omim.org/entry/609536 609536]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.  Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele (PubMed:15995705).
 == Function ==
-[https://www.uniprot.org/uniprot/CO6_HUMAN CO6_HUMAN] Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.
+[https://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN] Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled.  Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryo-electron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming beta-hairpins of C8 to form an intermolecular beta-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 beta-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells.
+Structural basis for membrane attack complex inhibition by CD59.,Couves EC, Gardner S, Voisin TB, Bickel JK, Stansfeld PJ, Tate EW, Bubeck D Nat Commun. 2023 Feb 16;14(1):890. doi: 10.1038/s41467-023-36441-z. PMID:36797260<ref>PMID:36797260</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8b0f" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>