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1jrh

From Proteopedia

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Revision as of 08:41, 17 January 2018

COMPLEX (ANTIBODY/ANTIGEN)

Structural highlights

1jrh is a 3 chain structure with sequence from Human and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CDNA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[INGR1_HUMAN] Defects in IFNGR1 are a cause of Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance.^[1] ^[2]

Function

[INGR1_HUMAN] Receptor for interferon gamma. Two receptors bind one interferon gamma dimer.

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

The extracellular interferon gamma receptor alpha-chain comprises two immunoglobulin-like domains, each with fibronectin type-III topology, which are responsible for binding interferon gamma at the cell surface. The epitopes on the human receptor recognized by three neutralizing antibodies, A6, gammaR38 and gammaR99, have been mapped by homolog scanning mutagenesis. In this way, a loop connecting beta-strands C and C' in the N-terminal domain was identified as a key component of the epitopes bound by A6 and gammaR38, whereas gammaR99 binds to the C-terminal domain in a region including strands A and B and part of the large C'E loop. The epitope for A6 was confirmed in a crystal structure of a complex between a recombinant N-terminal receptor domain and the Fab fragment from A6, determined by X-ray diffraction to 2.8 A resolution. The antibody-antigen interface buries 1662 A2 of protein surface, including 22 antibody residues from five complementarity determining regions, primarily through interactions with the CC' surface loop of the receptor. The floor of the antigen binding cavity is formed mainly by residues from CDR L3 and CDR H3 while a surrounding ridge is formed by residues from all other CDRs except L2. Many potential polar interactions, as well as 13 aromatic side-chains, four in VL, six in VH and three in the receptor, are situated at the interface. The surface of the receptor contacted by A6 overlaps to a large extent with that contacted by interferon-gamma, in the ligand-receptor complex. However, the conformation of this epitope is very different in the two complexes, demonstrating that conformational mobility in a surface loop on this cytokine receptor permits steric and electrostatic complementarity to two quite differently shaped binding sites.

Neutralizing epitopes on the extracellular interferon gamma receptor (IFNgammaR) alpha-chain characterized by homolog scanning mutagenesis and X-ray crystal structure of the A6 fab-IFNgammaR1-108 complex.,Sogabe S, Stuart F, Henke C, Bridges A, Williams G, Birch A, Winkler FK, Robinson JA J Mol Biol. 1997 Nov 7;273(4):882-97. PMID:9367779^[3]

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

References

↑ Jouanguy E, Lamhamedi-Cherradi S, Altare F, Fondaneche MC, Tuerlinckx D, Blanche S, Emile JF, Gaillard JL, Schreiber R, Levin M, Fischer A, Hivroz C, Casanova JL. Partial interferon-gamma receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guerin infection and a sibling with clinical tuberculosis. J Clin Invest. 1997 Dec 1;100(11):2658-64. PMID:9389728 doi:10.1172/JCI119810
↑ Jouanguy E, Dupuis S, Pallier A, Doffinger R, Fondaneche MC, Fieschi C, Lamhamedi-Cherradi S, Altare F, Emile JF, Lutz P, Bordigoni P, Cokugras H, Akcakaya N, Landman-Parker J, Donnadieu J, Camcioglu Y, Casanova JL. In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma. J Clin Invest. 2000 May;105(10):1429-36. PMID:10811850 doi:10.1172/JCI9166
↑ Sogabe S, Stuart F, Henke C, Bridges A, Williams G, Birch A, Winkler FK, Robinson JA. Neutralizing epitopes on the extracellular interferon gamma receptor (IFNgammaR) alpha-chain characterized by homolog scanning mutagenesis and X-ray crystal structure of the A6 fab-IFNgammaR1-108 complex. J Mol Biol. 1997 Nov 7;273(4):882-97. PMID:9367779 doi:10.1006/jmbi.1997.1336

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/1jrh"

@@ Line 1: / Line 1: @@
 ==COMPLEX (ANTIBODY/ANTIGEN)==
 <StructureSection load='1jrh' size='340' side='right' caption='[[1jrh]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1jrh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JRH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JRH FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1jrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jrh OCA], [http://pdbe.org/1jrh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jrh RCSB], [http://www.ebi.ac.uk/pdbsum/1jrh PDBsum]</span></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=1jrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jrh OCA], [http://pdbe.org/1jrh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jrh RCSB], [http://www.ebi.ac.uk/pdbsum/1jrh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jrh ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jr/1jrh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jr/1jrh_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 32: @@
 ==See Also==
-*[[Antibody|Antibody]]
+*[[3D structures of antibody|3D structures of antibody]]
-*[[Interferon receptor|Interferon receptor]]
 == References ==
 <references/>

1jrh

From Proteopedia

Revision as of 08:41, 17 January 2018

COMPLEX (ANTIBODY/ANTIGEN)

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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