4e0s

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Revision as of 07:58, 15 November 2017

Crystal Structure of C5b-6

Structural highlights

4e0s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CO5_HUMAN] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM: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). [CO6_HUMAN] Defects in C6 are the cause of complement component 6 deficiency (C6D) [MIM:612446]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.

Function

[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). [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.

Publication Abstract from PubMed

The complement Membrane Attack Complex (MAC) forms transmembrane pores in pathogen membranes. The first step in MAC assembly is cleavage of C5 to generate metastable C5b, which forms a stable complex with C6, termed C5b-6. C5b-6 initiates pore formation via the sequential recruitment of homologous proteins: C7, C8, and 12-18 copies of C9, each of which comprise a central MACPF domain flanked by auxiliary domains. We recently proposed a model of pore assembly, in which the auxiliary domains play key roles, both in stabilizing the closed conformation of the protomers, and in driving the sequential opening of the MACPF beta-sheet of each new recruit to the growing pore. Here, we describe an atomic model of C5b-6 at 4.2 A resolution. We show that C5b provides 4 interfaces for the auxiliary domains of C6. The largest interface is created by the insertion of an interdomain linker from C6 into a hydrophobic groove created by a major reorganization of the alpha-helical domain of C5b. In combination with a rigid-body docking of N-terminal elements of both proteins, C5b becomes locked into a stable conformation. Both C6 auxiliary domains flanking the linker pack tightly against C5b. The net effect is to induce a clockwise rigid-body rotation of 4 auxiliary domains as well as an opening/twisting of the central beta-sheet of C6, in the directions predicted by our model to activate or prime C6 for the subsequent steps in MAC assembly. The complex also suggests novel small-molecule strategies for modulating pathological MAC assembly.

Crystal structure of C5b-6 suggests a structural basis for priming the assembly of the Membrane Attack Complex (MAC).,Aleshin AE, Discipio RG, Stec B, Liddington RC J Biol Chem. 2012 Apr 12. PMID:22500023^[1]

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

References

↑ Aleshin AE, Discipio RG, Stec B, Liddington RC. Crystal structure of C5b-6 suggests a structural basis for priming the assembly of the Membrane Attack Complex (MAC). J Biol Chem. 2012 Apr 12. PMID:22500023 doi:10.1074/jbc.M112.361121

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4e0s"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4e0s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E0S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E0S 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e0s OCA], [http://pdbe.org/4e0s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e0s RCSB], [http://www.ebi.ac.uk/pdbsum/4e0s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e0s ProSAT]</span></td></tr>
 </table>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4e0s" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Complement C5|Complement C5]]
 == References ==
 <references/>

4e0s

From Proteopedia

Revision as of 07:58, 15 November 2017

Crystal Structure of C5b-6

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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