7b26

From Proteopedia

(Difference between revisions)

Current revision

CirpA1 in complex with pseudo-monomeric Properdin lacking TSR2-3

Structural highlights

7b26 is a 3 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.
Method:	X-ray diffraction, Resolution 3.4Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PROP_HUMAN Defects in CFP are the cause of properdin deficiency (PFD) [MIM:312060. PFD results in higher susceptibility to bacterial infections; especially to meningococcal infections. Three phenotypes have been reported: complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin (type III).^[1] ^[2] ^[3]

Function

PROP_HUMAN A positive regulator of the alternate pathway of complement. It binds to and stabilizes the C3- and C5-convertase enzyme complexes.

Publication Abstract from PubMed

Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.

Structure and function of a family of tick-derived complement inhibitors targeting properdin.,Braunger K, Ahn J, Jore MM, Johnson S, Tang TTL, Pedersen DV, Andersen GR, Lea SM Nat Commun. 2022 Jan 14;13(1):317. doi: 10.1038/s41467-021-27920-2. PMID:35031611^[4]

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

References

↑ Fredrikson GN, Westberg J, Kuijper EJ, Tijssen CC, Sjoholm AG, Uhlen M, Truedsson L. Molecular characterization of properdin deficiency type III: dysfunction produced by a single point mutation in exon 9 of the structural gene causing a tyrosine to aspartic acid interchange. J Immunol. 1996 Oct 15;157(8):3666-71. PMID:8871668
↑ Fredrikson GN, Gullstrand B, Westberg J, Sjoholm AG, Uhlen M, Truedsson L. Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations. J Clin Immunol. 1998 Jul;18(4):272-82. PMID:9710744
↑ van den Bogaard R, Fijen CA, Schipper MG, de Galan L, Kuijper EJ, Mannens MM. Molecular characterisation of 10 Dutch properdin type I deficient families: mutation analysis and X-inactivation studies. Eur J Hum Genet. 2000 Jul;8(7):513-8. PMID:10909851 doi:10.1038/sj.ejhg.5200496
↑ Braunger K, Ahn J, Jore MM, Johnson S, Tang TTL, Pedersen DV, Andersen GR, Lea SM. Structure and function of a family of tick-derived complement inhibitors targeting properdin. Nat Commun. 2022 Jan 14;13(1):317. doi: 10.1038/s41467-021-27920-2. PMID:35031611 doi:http://dx.doi.org/10.1038/s41467-021-27920-2

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/7b26"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7b26 is ON HOLD
+==CirpA1 in complex with pseudo-monomeric Properdin lacking TSR2-3==
+<StructureSection load='7b26' size='340' side='right'caption='[[7b26]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7b26]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rhipicephalus_pulchellus Rhipicephalus pulchellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B26 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7b26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b26 OCA], [https://pdbe.org/7b26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b26 RCSB], [https://www.ebi.ac.uk/pdbsum/7b26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b26 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PROP_HUMAN PROP_HUMAN] Defects in CFP are the cause of properdin deficiency (PFD) [MIM:[https://omim.org/entry/312060 312060]. PFD results in higher susceptibility to bacterial infections; especially to meningococcal infections. Three phenotypes have been reported: complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin (type III).<ref>PMID:8871668</ref> <ref>PMID:9710744</ref> <ref>PMID:10909851</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PROP_HUMAN PROP_HUMAN] A positive regulator of the alternate pathway of complement. It binds to and stabilizes the C3- and C5-convertase enzyme complexes.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.
-Authors: Lea, S.M., Johnson, S., Braunger, K.
+Structure and function of a family of tick-derived complement inhibitors targeting properdin.,Braunger K, Ahn J, Jore MM, Johnson S, Tang TTL, Pedersen DV, Andersen GR, Lea SM Nat Commun. 2022 Jan 14;13(1):317. doi: 10.1038/s41467-021-27920-2. PMID:35031611<ref>PMID:35031611</ref>
-Description: CirpA1 in complex with pseudo-monomeric Properdin lacking TSR2-3
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Braunger, K]]
+<div class="pdbe-citations 7b26" style="background-color:#fffaf0;"></div>
-[[Category: Johnson, S]]
+== References ==
-[[Category: Lea, S.M]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Rhipicephalus pulchellus]]
+[[Category: Braunger K]]
+[[Category: Johnson S]]
+[[Category: Lea SM]]

7b26

From Proteopedia

Current revision

CirpA1 in complex with pseudo-monomeric Properdin lacking TSR2-3

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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