1adq: Difference between revisions

Revision as of 12:43, 21 February 2008

CRYSTAL STRUCTURE OF A HUMAN IGM RHEUMATOID FACTOR FAB IN COMPLEX WITH ITS AUTOANTIGEN IGG FC

OverviewOverview

Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis, which bind to the Fc regions of IgG molecules. Here we report the crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial Fc-binding proteins. The antibody residues involved in autorecognition are all located at the edge of the conventional combining site surface, leaving much of the latter available, potentially, for recognition of a different antigen. Since an important contact residue is somatic mutation, the structure implicates antigen-driven selection, following somatic mutation of germline genes, in the production of pathogenic rheumatoid factors.

About this StructureAbout this Structure

1ADQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction., Corper AL, Sohi MK, Bonagura VR, Steinitz M, Jefferis R, Feinstein A, Beale D, Taussig MJ, Sutton BJ, Nat Struct Biol. 1997 May;4(5):374-81. PMID:9145108

Page seeded by OCA on Thu Feb 21 11:43:24 2008

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OCA

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-[[Image:1adq.gif|left|200px]]<br />
+[[Image:1adq.gif|left|200px]]<br /><applet load="1adq" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1adq" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1adq, resolution 3.15&Aring;" />
 '''CRYSTAL STRUCTURE OF A HUMAN IGM RHEUMATOID FACTOR FAB IN COMPLEX WITH ITS AUTOANTIGEN IGG FC'''<br />
 ==Overview==
-Rheumatoid factors are the characteristic autoantibodies of rheumatoid, arthritis, which bind to the Fc regions of IgG molecules. Here we report, the crystal structure of the Fab fragment of a patient-derived IgM, rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A, resolution. This is the first structure of an autoantibody-autoantigen, complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3, cleft region, and overlaps the binding sites of bacterial Fc-binding, proteins. The antibody residues involved in autorecognition are all, located at the edge of the conventional combining site surface, leaving, much of the latter available, potentially, for recognition of a different, antigen. Since an important contact residue is somatic mutation, the, structure implicates antigen-driven selection, following somatic mutation, of germline genes, in the production of pathogenic rheumatoid factors.
+Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis, which bind to the Fc regions of IgG molecules. Here we report the crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial Fc-binding proteins. The antibody residues involved in autorecognition are all located at the edge of the conventional combining site surface, leaving much of the latter available, potentially, for recognition of a different antigen. Since an important contact residue is somatic mutation, the structure implicates antigen-driven selection, following somatic mutation of germline genes, in the production of pathogenic rheumatoid factors.
 ==About this Structure==
-ADQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ADQ OCA].
+ADQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ADQ OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Corper, A.L.]]
+[[Category: Corper, A L.]]
-[[Category: Sutton, B.J.]]
+[[Category: Sutton, B J.]]
-[[Category: Taussig, M.J.]]
+[[Category: Taussig, M J.]]
 [[Category: complex (immunoglobulin/autoantigen)]]
 [[Category: rheumatoid factor auto-antibody complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:57:48 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:43:24 2008''