View source for 6h04


==Closed conformation of the Membrane Attack Complex==
<SX load='6h04' size='340' side='right' viewer='molstar' caption='[[6h04]], [[Resolution|resolution]] 5.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6h04]] is a 24 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=6H04 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H04 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6h03|6h03]]</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=6h04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h04 OCA], [http://pdbe.org/6h04 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h04 RCSB], [http://www.ebi.ac.uk/pdbsum/6h04 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h04 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CO8A_HUMAN CO8A_HUMAN]] Defects in C8A are a cause of complement component 8 deficiency type 1 (C8D1) [MIM:[http://omim.org/entry/613790 613790]]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. [[http://www.uniprot.org/uniprot/CO8B_HUMAN CO8B_HUMAN]] Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CO6_HUMAN CO6_HUMAN]] Defects in C6 are the cause of complement component 6 deficiency (C6D) [MIM:[http://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. [[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[http://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). [[http://www.uniprot.org/uniprot/CO9_HUMAN CO9_HUMAN]] Age-related macular degeneration;Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry.  Disease susceptibility is associated with variations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CO7_HUMAN CO7_HUMAN]] Immunodeficiency due to a late component of complement deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry. 
== Function ==
[[http://www.uniprot.org/uniprot/CO8A_HUMAN CO8A_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. C8A inserts into the target membrane, but does not form pores by itself.<ref>PMID:7440581</ref> <ref>PMID:17872444</ref>  [[http://www.uniprot.org/uniprot/CO8B_HUMAN CO8B_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. [[http://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. [[http://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). [[http://www.uniprot.org/uniprot/CO9_HUMAN CO9_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. C9 is the pore-forming subunit of the MAC. [[http://www.uniprot.org/uniprot/CO7_HUMAN CO7_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. C7 serves as a membrane anchor. [[http://www.uniprot.org/uniprot/CO8G_HUMAN CO8G_HUMAN]] C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The membrane attack complex (MAC) is one of the immune system's first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant beta-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how beta-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions.

CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.,Menny A, Serna M, Boyd CM, Gardner S, Joseph AP, Morgan BP, Topf M, Brooks NJ, Bubeck D Nat Commun. 2018 Dec 14;9(1):5316. doi: 10.1038/s41467-018-07653-5. PMID:30552328<ref>PMID:30552328</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6h04" style="background-color:#fffaf0;"></div>

==See Also==
*[[Complement C5 3D structures|Complement C5 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boyd, C M]]
[[Category: Bubeck, D]]
[[Category: Gardner, S]]
[[Category: Joseph, A P]]
[[Category: Menny, A]]
[[Category: Serna, M]]
[[Category: Topf, M]]
[[Category: C5b9]]
[[Category: Immune system]]