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3km9

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Revision as of 07:17, 7 August 2019

Structure of complement C5 in complex with the C-terminal beta-grasp domain of SSL7

Structural highlights

3km9 is a 4 chain structure with sequence from Homo sapiens and Staae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3cu7, 2qej, 3kls
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).

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).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion strategy. The protein binds both complement C5 and IgA, yet it is unclear whether SSL7 cross-links these two proteins and, if so, what purpose this serves the pathogen. We have isolated a stable IgA-SSL7-C5 complex, and our crystal structure of the C5-SSL7 complex confirms that binding to C5 occurs exclusively through the C-terminal beta-grasp domain of SSL7 leaving the OB domain free to interact with IgA. SSL7 interacts with C5 >70 A from the C5a cleavage site without inducing significant conformational changes in C5, and efficient inhibition of convertase cleavage of C5 is shown to be IgA dependent. Inhibition of C5a production and bacteriolysis are all shown to require C5 and IgA binding while inhibition of hemolysis is achieved by the C5 binding SSL7 beta-grasp domain alone. These results provide a conceptual and structural basis for the development of a highly specific complement inhibitor preventing only the formation of the lytic membrane attack complex without affecting the important signaling functions of C5a.

Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus.,Laursen NS, Gordon N, Hermans S, Lorenz N, Jackson N, Wines B, Spillner E, Christensen JB, Jensen M, Fredslund F, Bjerre M, Sottrup-Jensen L, Fraser JD, Andersen GR Proc Natl Acad Sci U S A. 2010 Feb 4. PMID:20133685^[1]

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

References

↑ Laursen NS, Gordon N, Hermans S, Lorenz N, Jackson N, Wines B, Spillner E, Christensen JB, Jensen M, Fredslund F, Bjerre M, Sottrup-Jensen L, Fraser JD, Andersen GR. Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus. Proc Natl Acad Sci U S A. 2010 Feb 4. PMID:20133685

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3km9"

@@ Line 1: / Line 1: @@
 ==Structure of complement C5 in complex with the C-terminal beta-grasp domain of SSL7==
-<StructureSection load='3km9' size='340' side='right' caption='[[3km9]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
+<StructureSection load='3km9' size='340' side='right'caption='[[3km9]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3km9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staae Staae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KM9 FirstGlance]. <br>
@@ Line 16: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3km9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3km9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 3km9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Complement C5 3D structures|Complement C5 3D structures]]
 == References ==
 <references/>
@@ Line 36: / Line 39: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Staae]]
 [[Category: Andersen, G R]]

3km9

From Proteopedia

Revision as of 07:17, 7 August 2019

Structure of complement C5 in complex with the C-terminal beta-grasp domain of SSL7

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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