5xmh

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Revision as of 05:54, 16 May 2018

Crystal structure of an IgM rheumatoid factor YES8c in complex with IgG1 Fc

Structural highlights

5xmh 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:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IGG1_HUMAN] Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Rheumatoid factors (RFs) are autoantibodies against the fragment-crystallizable (Fc) region of immunoglobulin G (IgG). In individuals with hematological diseases such as cryoglobulinemia and certain B-cell lymphoma forms, the RFs derived from specific heavy- and light-chain germline pairs, so-called "stereotypic RFs," are frequently produced in copious amounts and form immune complexes with IgG in serum. Of note, many structural details of the antigen-recognition mechanisms in RFs are unclear. Here, we report the crystal structure of the RF YES8c derived from the IGHV1-69/IGKV3-20 germline pair, the commonest of the stereotypic RFs, in complex with human IgG1-Fc at 2.8 A resolution. We observed that YES8c binds to the CH2-CH3 elbow in the canonical antigen-binding manner involving a large antigen-antibody interface. On the basis of this observation combined with mutational analyses, we propose a recognition mechanism common to IGHV1-69/IGKV3-20 RFs: (1) the interaction of the Leu432-His435 region of Fc enables the highly variable complementarity-determining region (CDR)-H3 to participate in the binding, (2) the hydrophobic tip in the CDR-H2 typical of IGHV1-69 antibodies recognizes the hydrophobic patch on Fc, and (3) the interaction of the highly conserved RF light chain with Fc is important for RF activity. These features may determine the putative epitope common to the IGHV1-69/IGKV3-20 RFs. We also showed that some mutations in the binding site of RF increase the affinity to Fc, which may aggravate the hematological diseases. Our findings unravel the structural basis for germline-encoded antibody autoreactivity.

Structure-function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity.,Shiroishi M, Ito Y, Shimokawa K, Lee JM, Kusakabe T, Ueda T J Biol Chem. 2018 Mar 9. pii: M117.814475. doi: 10.1074/jbc.M117.814475. PMID:29523691^[4]

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

References

↑ Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107-20. PMID:17576170 doi:http://dx.doi.org/10.1146/annurev.genet.41.110306.130340
↑ Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52. doi:, 10.1016/j.jaci.2009.09.046. PMID:20176268 doi:http://dx.doi.org/10.1016/j.jaci.2009.09.046
↑ McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128. PMID:22158414 doi:http://dx.doi.org/10.1038/nri3128
↑ Shiroishi M, Ito Y, Shimokawa K, Lee JM, Kusakabe T, Ueda T. Structure-function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity. J Biol Chem. 2018 Mar 9. pii: M117.814475. doi: 10.1074/jbc.M117.814475. PMID:29523691 doi:http://dx.doi.org/10.1074/jbc.M117.814475

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xmh"

@@ Line 3: / Line 3: @@
 <StructureSection load='5xmh' size='340' side='right' caption='[[5xmh]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xmh]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XMH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XMH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xmh]] 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=5XMH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XMH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5xmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xmh OCA], [http://pdbe.org/5xmh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xmh RCSB], [http://www.ebi.ac.uk/pdbsum/5xmh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xmh ProSAT]</span></td></tr>
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Kusakabe, M]]
 [[Category: Lee, J M]]

5xmh

From Proteopedia

Revision as of 05:54, 16 May 2018

Crystal structure of an IgM rheumatoid factor YES8c in complex with IgG1 Fc

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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