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6rqj

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Structure of human complement C5 complexed with tick inhibitors OmCI, RaCI1 and CirpT1

6rqj, resolution 3.50Å

Structural highlights

6rqj is a 5 chain structure with sequence from Homo sapiens and Rhipicephalus pulchellus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	6rpt
Experimental data:	Check to display Experimental Data
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).

Publication Abstract from PubMed

The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick Rhipicephalus pulchellus lasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5-CirpT complex by cryoelectron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4-CirpT complex was solved by X-ray crystallography (at 2.7 A). We thus present the fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway.

An inhibitor of complement C5 provides structural insights into activation.,Reichhardt MP, Johnson S, Tang T, Morgan T, Tebeka N, Popitsch N, Deme JC, Jore MM, Lea SM Proc Natl Acad Sci U S A. 2019 Dec 23. pii: 1909973116. doi:, 10.1073/pnas.1909973116. PMID:31871188^[1]

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

References

↑ Reichhardt MP, Johnson S, Tang T, Morgan T, Tebeka N, Popitsch N, Deme JC, Jore MM, Lea SM. An inhibitor of complement C5 provides structural insights into activation. Proc Natl Acad Sci U S A. 2019 Dec 23. pii: 1909973116. doi:, 10.1073/pnas.1909973116. PMID:31871188 doi:http://dx.doi.org/10.1073/pnas.1909973116

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/6rqj"

@@ Line 3: / Line 3: @@
 <SX load='6rqj' size='340' side='right' viewer='molstar' caption='[[6rqj]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rqj]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rhipicephalus_pulchellus Rhipicephalus pulchellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RQJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rqj]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rhipicephalus_pulchellus Rhipicephalus pulchellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RQJ 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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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">[[6rpt|6rpt]]</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=6rqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rqj OCA], [http://pdbe.org/6rqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rqj RCSB], [http://www.ebi.ac.uk/pdbsum/6rqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rqj ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rqj OCA], [http://pdbe.org/6rqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rqj RCSB], [http://www.ebi.ac.uk/pdbsum/6rqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rqj ProSAT]</span></td></tr>
 </table>
 == Disease ==

6rqj

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Current revision

Structure of human complement C5 complexed with tick inhibitors OmCI, RaCI1 and CirpT1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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