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3ojy

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Revision as of 18:05, 14 August 2019

Crystal Structure of Human Complement Component C8

Structural highlights

3ojy is a 3 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:	,
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CO8A_HUMAN] Defects in C8A are a cause of complement component 8 deficiency type 1 (C8D1) [MIM:613790]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. [CO8B_HUMAN] Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry.

Function

[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.^[1] ^[2] [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. [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.

Publication Abstract from PubMed

C8 is one of five complement proteins that assemble on bacterial membranes to form the lethal pore-like "membrane attack complex" (MAC) of complement. The MAC consists of one C5b, C6, C7, and C8 and 12-18 molecules of C9. C8 is composed of three genetically distinct subunits, C8alpha, C8beta, and C8gamma. The C6, C7, C8alpha, C8beta, and C9 proteins are homologous and together comprise the MAC family of proteins. All contain N- and C-terminal modules and a central 40-kDa membrane attack complex perforin (MACPF) domain that has a key role in forming the MAC pore. Here, we report the 2.5 A resolution crystal structure of human C8 purified from blood. This is the first structure of a MAC family member and of a human MACPF-containing protein. The structure shows the modules in C8alpha and C8beta are located on the periphery of C8 and not likely to interact with the target membrane. The C8gamma subunit, a member of the lipocalin family of proteins that bind and transport small lipophilic molecules, shows no occupancy of its putative ligand-binding site. C8alpha and C8beta are related by a rotation of approximately 22 degrees with only a small translational component along the rotation axis. Evolutionary arguments suggest the geometry of binding between these two subunits is similar to the arrangement of C9 molecules within the MAC pore. This leads to a model of the MAC that explains how C8-C9 and C9-C9 interactions could facilitate refolding and insertion of putative MACPF transmembrane beta-hairpins to form a circular pore.

Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement.,Lovelace LL, Cooper CL, Sodetz JM, Lebioda L J Biol Chem. 2011 May 20;286(20):17585-92. Epub 2011 Mar 25. PMID:21454577^[3]

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

References

↑ Steckel EW, York RG, Monahan JB, Sodetz JM. The eighth component of human complement. Purification and physicochemical characterization of its unusual subunit structure. J Biol Chem. 1980 Dec 25;255(24):11997-2005. PMID:7440581
↑ Hadders MA, Beringer DX, Gros P. Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science. 2007 Sep 14;317(5844):1552-4. PMID:17872444 doi:317/5844/1552
↑ Lovelace LL, Cooper CL, Sodetz JM, Lebioda L. Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement. J Biol Chem. 2011 May 20;286(20):17585-92. Epub 2011 Mar 25. PMID:21454577 doi:10.1074/jbc.M111.219766

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/3ojy"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Complement Component C8==
-<StructureSection load='3ojy' size='340' side='right' caption='[[3ojy]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
+<StructureSection load='3ojy' size='340' side='right'caption='[[3ojy]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3ojy]] is a 3 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=3OJY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OJY FirstGlance]. <br>
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Cooper, C L]]
 [[Category: Lebioda, L]]

3ojy

From Proteopedia

Revision as of 18:05, 14 August 2019

Crystal Structure of Human Complement Component C8

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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