2vxs

From Proteopedia

(Difference between revisions)

Revision as of 15:36, 13 December 2023

Structure of IL-17A in complex with a potent, fully human neutralising antibody

Structural highlights

2vxs is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.63Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL17_HUMAN Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts.

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

IL-17A is a pro-inflammatory cytokine produced by the newly identified Th17 subset of T-cells. We have isolated a human monoclonal antibody to IL-17A (CAT-2200) that can potently neutralize the effects of recombinant and native human IL-17A. We determined the crystal structure of IL-17A in complex with the CAT-2200 Fab at 2.6 A resolution in order to provide a definitive characterization of the epitope and paratope regions. Approximately a third of the IL-17A dimer is disordered in this crystal structure. The disorder occurs in both independent copies of the complex in the asymmetric unit and does not appear to be influenced by crystal packing. The complex contains one IL-17A dimer sandwiched between two CAT-2200 Fab fragments. The IL-17A is a disulfide-linked homodimer that is similar in structure to IL-17F, adopting a cystine-knot fold. The structure is not inconsistent with the previous prediction of a receptor binding cavity on IL-17 family members. The epitope recognized by CAT-2200 is shown to involve 12 amino acid residues from the quaternary structure of IL-17A, with each Fab contacting both monomers in the dimer. All complementarity-determining regions (CDRs) in the Fab contribute to a total of 16 amino acid residues in the antibody paratope. In vitro affinity optimization was used to generate CAT-2200 from a parental lead antibody using random mutagenesis of CDR3 loops. This resulted in seven amino acid changes (three in VL-CDR3 and four in VH-CDR3) and gave an approximate 30-fold increase in potency in a cell-based neutralization assay. Two of the seven amino acids form part of the CAT-2200 paratope. The observed interaction site between CAT-2200 and IL-17A is consistent with data from hydrogen/deuterium exchange mass spectrometry and mutagenesis approaches.

Structure of IL-17A in complex with a potent, fully human neutralizing antibody.,Gerhardt S, Abbott WM, Hargreaves D, Pauptit RA, Davies RA, Needham MR, Langham C, Barker W, Aziz A, Snow MJ, Dawson S, Welsh F, Wilkinson T, Vaugan T, Beste G, Bishop S, Popovic B, Rees G, Sleeman M, Tuske SJ, Coales SJ, Hamuro Y, Russell C J Mol Biol. 2009 Dec 18;394(5):905-21. Epub 2009 Oct 14. PMID:19835883^[1]

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

References

↑ Gerhardt S, Abbott WM, Hargreaves D, Pauptit RA, Davies RA, Needham MR, Langham C, Barker W, Aziz A, Snow MJ, Dawson S, Welsh F, Wilkinson T, Vaugan T, Beste G, Bishop S, Popovic B, Rees G, Sleeman M, Tuske SJ, Coales SJ, Hamuro Y, Russell C. Structure of IL-17A in complex with a potent, fully human neutralizing antibody. J Mol Biol. 2009 Dec 18;394(5):905-21. Epub 2009 Oct 14. PMID:19835883 doi:10.1016/j.jmb.2009.10.008

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vxs"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vxs' size='340' side='right'caption='[[2vxs]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vxs]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vxs]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.63&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2vxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxs OCA], [https://pdbe.org/2vxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxs RCSB], [https://www.ebi.ac.uk/pdbsum/2vxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxs ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Abbott, W M]]
+[[Category: Abbott WM]]
-[[Category: Aziz, A]]
+[[Category: Aziz A]]
-[[Category: Barker, W]]
+[[Category: Barker W]]
-[[Category: Bell, P]]
+[[Category: Bell P]]
-[[Category: Coales, S J]]
+[[Category: Coales SJ]]
-[[Category: Davies, R A]]
+[[Category: Davies RA]]
-[[Category: Dawson, S]]
+[[Category: Dawson S]]
-[[Category: Gerhardt, S]]
+[[Category: Gerhardt S]]
-[[Category: Hamuro, Y]]
+[[Category: Hamuro Y]]
-[[Category: Hargreaves, D]]
+[[Category: Hargreaves D]]
-[[Category: Langham, C]]
+[[Category: Langham C]]
-[[Category: Needham, M R.C]]
+[[Category: Needham MRC]]
-[[Category: Pauptit, R A]]
+[[Category: Pauptit RA]]
-[[Category: Russell, C]]
+[[Category: Russell C]]
-[[Category: Smith, M J]]
+[[Category: Smith MJ]]
-[[Category: Tuske, S J]]
+[[Category: Tuske SJ]]
-[[Category: Welsh, F]]
+[[Category: Welsh F]]
-[[Category: Antibody]]
-[[Category: Complex]]
-[[Category: Cytokine]]
-[[Category: Epitope]]
-[[Category: Glycoprotein]]
-[[Category: Interleukin-17]]
-[[Category: Secreted]]

2vxs

From Proteopedia

Revision as of 15:36, 13 December 2023

Structure of IL-17A in complex with a potent, fully human neutralising antibody

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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