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2j6e

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Revision as of 06:32, 11 July 2018

Crystal Structure of an Autoimmune Complex between a Human IgM Rheumatoid Factor and IgG1 Fc reveals a Novel Fc Epitope and Evidence for Affinity Maturation

Structural highlights

2j6e is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , , , , ,
Related:	1aj7, 1aqk, 1d5b, 1d5i, 1d6v, 1dn2, 1e4k, 1fc1, 1fc2, 1fcc, 1h3t, 1h3u, 1h3v, 1h3w, 1h3y, 1hzh, 1i7z, 1iis, 1iix, 1l6x, 1n7m, 1oqx, 1t83, 2iwg, 2rcs
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.

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

Rheumatoid factors (RF) are autoantibodies that recognize epitopes in the Fc region of immunoglobulin (Ig) G and that correlate with the clinical severity of rheumatoid arthritis (RA). Here we report the X-ray crystallographic structure, at 3 A resolution, of a complex between the Fc region of human IgG1 and the Fab fragment of a monoclonal IgM RF (RF61), derived from an RA patient and with a relatively high affinity for IgG Fc. In the complex, two Fab fragments bind to each Fc at epitopes close to the C terminus, and each epitope comprises residues from both Cgamma3 domains. A central role in the unusually hydrophilic epitope is played by the side-chain of Arg355, accounting for the subclass specificity of RF61, which recognizes IgG1,-2, and -3 in preference to IgG4, in which the corresponding residue is Gln355. Compared with a previously determined complex of a lower affinity RF (RF-AN) bound to IgG4 Fc, in which only residues at the very edge of the antibody combining site were involved in binding, the epitope bound by RF61 is centered in classic fashion on the axis of the V(H):V(L) beta-barrel. The complementarity determining region-H3 loop plays a key role, forming a pocket in which Arg355 is bound by two salt-bridges. The antibody contacts also involve two somatically mutated V(H) residues, reinforcing the suggestion of a process of antigen-driven maturation and selection for IgG Fc during the generation of this RF autoantibody.

Crystal structure of a human autoimmune complex between IgM rheumatoid factor RF61 and IgG1 Fc reveals a novel epitope and evidence for affinity maturation.,Duquerroy S, Stura EA, Bressanelli S, Fabiane SM, Vaney MC, Beale D, Hamon M, Casali P, Rey FA, Sutton BJ, Taussig MJ J Mol Biol. 2007 May 18;368(5):1321-31. Epub 2007 Mar 6. PMID:17395205^[1]

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

References

↑ Duquerroy S, Stura EA, Bressanelli S, Fabiane SM, Vaney MC, Beale D, Hamon M, Casali P, Rey FA, Sutton BJ, Taussig MJ. Crystal structure of a human autoimmune complex between IgM rheumatoid factor RF61 and IgG1 Fc reveals a novel epitope and evidence for affinity maturation. J Mol Biol. 2007 May 18;368(5):1321-31. Epub 2007 Mar 6. PMID:17395205 doi:10.1016/j.jmb.2007.02.085

1 Structural highlights
2 Disease
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/2j6e"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF AN AUTOIMMUNE COMPLEX BETWEEN A HUMAN IGM RHEUMATOID FACTOR AND IGG1 FC REVEALS A NOVEL FC EPITOPE AND EVIDENCE FOR AFFINITY MATURATION==
+==Crystal Structure of an Autoimmune Complex between a Human IgM Rheumatoid Factor and IgG1 Fc reveals a Novel Fc Epitope and Evidence for Affinity Maturation==
 <StructureSection load='2j6e' size='340' side='right' caption='[[2j6e]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2j6e]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J6E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aj7|1aj7]], [[1aqk|1aqk]], [[1d5b|1d5b]], [[1d5i|1d5i]], [[1d6v|1d6v]], [[1dn2|1dn2]], [[1e4k|1e4k]], [[1fc1|1fc1]], [[1fc2|1fc2]], [[1fcc|1fcc]], [[1h3t|1h3t]], [[1h3u|1h3u]], [[1h3v|1h3v]], [[1h3w|1h3w]], [[1h3y|1h3y]], [[1hzh|1hzh]], [[1i7z|1i7z]], [[1iis|1iis]], [[1iix|1iix]], [[1l6x|1l6x]], [[1n7m|1n7m]], [[1oqx|1oqx]], [[1t83|1t83]], [[2iwg|2iwg]], [[2rcs|2rcs]]</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=2j6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6e OCA], [http://pdbe.org/2j6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j6e RCSB], [http://www.ebi.ac.uk/pdbsum/2j6e 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=2j6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6e OCA], [http://pdbe.org/2j6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j6e RCSB], [http://www.ebi.ac.uk/pdbsum/2j6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6e ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j6/2j6e_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j6/2j6e_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 ==See Also==
-*[[Monoclonal Antibody|Monoclonal Antibody]]
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>

2j6e

From Proteopedia

Revision as of 06:32, 11 July 2018

Crystal Structure of an Autoimmune Complex between a Human IgM Rheumatoid Factor and IgG1 Fc reveals a Novel Fc Epitope and Evidence for Affinity Maturation

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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