9fmb

From Proteopedia

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Current revision

Crystal structure of human IgD-Fc

Structural highlights

9fmb is a 4 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 3Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IGHD_HUMAN Constant region of immunoglobulin heavy chains. 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:20176268, PubMed:22158414). 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:17576170, PubMed:20176268). IgD is the major antigen receptor isotype on the surface of most peripheral B-cells, where it is coexpressed with IgM. The membrane-bound IgD (mIgD) induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. Soluble IgD (sIgD) concentration in serum below those of IgG, IgA, and IgM but much higher than that of IgE. IgM and IgD molecules present on B cells have identical V regions and antigen-binding sites. After the antigen binds to the B-cell receptor, the secreted form sIgD is shut off. IgD is a potent inducer of TNF, IL1B, and IL1RN. IgD also induces release of IL6, IL10, and LIF from peripheral blood mononuclear cells. Monocytes seem to be the main producers of cytokines in vitro in the presence of IgD (PubMed:10702483, PubMed:11282392, PubMed:8774350).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Of the five human antibody isotypes, the function of IgD is the least well-understood, although various studies point to a role for IgD in mucosal immunity. IgD is also the least well structurally characterized isotype. Until recently, when crystal structures were reported for the IgD Fab, the only structural information available was a model for intact IgD based on solution scattering data. We now report the crystal structure of human IgD-Fc solved at 3.0 A resolution. Although similar in overall architecture to other human isotypes, IgD-Fc displays markedly different orientations of the Cdelta3 domains in the Cdelta3 domain dimer and the lowest interface area of all the human isotypes. The nature of the residues that form the dimer interface also differs from those conserved in the other isotypes. By contrast, the interface between the Cdelta2 and Cdelta3 domains in each chain is the largest among the human isotypes. This interface is characterized by two binding pockets, not seen in other isotypes, and points to a potential role for the Cdelta2/Cdelta3 interface in stabilizing the IgD-Fc homodimer. We investigated the thermal stability of IgD-Fc, alone and in the context of an intact IgD antibody, and found that IgD-Fc unfolds in a single transition. Human IgD-Fc clearly has unique structural features not seen in the other human isotypes, and comparison with other mammalian IgD sequences suggests that these unique features might be widely conserved.

The Crystal Structure of Human IgD-Fc Reveals Unexpected Differences With Other Antibody Isotypes.,Davies AM, Bui TTT, Pacheco-Gomez R, Vester SK, Beavil AJ, Gould HJ, Sutton BJ, McDonnell JM Proteins. 2024 Nov 25. doi: 10.1002/prot.26771. PMID:39582378^[7]

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

References

↑ Drenth JP, Goertz J, Daha MR, van der Meer JW. Immunoglobulin D enhances the release of tumor necrosis factor-alpha, and interleukin-1 beta as well as interleukin-1 receptor antagonist from human mononuclear cells. Immunology. 1996 Jul;88(3):355-62. PMID:8774350
↑ Vladutiu AO. Immunoglobulin D: properties, measurement, and clinical relevance. Clin Diagn Lab Immunol. 2000 Mar;7(2):131-40. PMID:10702483
↑ Preud'homme JL, Petit I, Barra A, Morel F, Lecron JC, Lelievre E. Structural and functional properties of membrane and secreted IgD. Mol Immunol. 2000 Oct;37(15):871-87. PMID:11282392
↑ 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
↑ Davies AM, Bui TTT, Pacheco-Gómez R, Vester SK, Beavil AJ, Gould HJ, Sutton BJ, McDonnell JM. The Crystal Structure of Human IgD-Fc Reveals Unexpected Differences With Other Antibody Isotypes. Proteins. 2024 Nov 25. PMID:39582378 doi:10.1002/prot.26771

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/9fmb"

Categories: Homo sapiens | Large Structures | Davies AM | McDonnell JM

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9fmb is ON HOLD
+==Crystal structure of human IgD-Fc==
+<StructureSection load='9fmb' size='340' side='right'caption='[[9fmb]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9fmb]] is a 4 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=9FMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FMB FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=9fmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fmb OCA], [https://pdbe.org/9fmb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fmb RCSB], [https://www.ebi.ac.uk/pdbsum/9fmb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fmb ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/IGHD_HUMAN IGHD_HUMAN] Constant region of immunoglobulin heavy chains. 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:20176268, PubMed:22158414). 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:17576170, PubMed:20176268). IgD is the major antigen receptor isotype on the surface of most peripheral B-cells, where it is coexpressed with IgM. The membrane-bound IgD (mIgD) induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. Soluble IgD (sIgD) concentration in serum below those of IgG, IgA, and IgM but much higher than that of IgE. IgM and IgD molecules present on B cells have identical V regions and antigen-binding sites. After the antigen binds to the B-cell receptor, the secreted form sIgD is shut off. IgD is a potent inducer of TNF, IL1B, and IL1RN. IgD also induces release of IL6, IL10, and LIF from peripheral blood mononuclear cells. Monocytes seem to be the main producers of cytokines in vitro in the presence of IgD (PubMed:10702483, PubMed:11282392, PubMed:8774350).<ref>PMID:8774350</ref> <ref>PMID:10702483</ref> <ref>PMID:11282392</ref> <ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Of the five human antibody isotypes, the function of IgD is the least well-understood, although various studies point to a role for IgD in mucosal immunity. IgD is also the least well structurally characterized isotype. Until recently, when crystal structures were reported for the IgD Fab, the only structural information available was a model for intact IgD based on solution scattering data. We now report the crystal structure of human IgD-Fc solved at 3.0 A resolution. Although similar in overall architecture to other human isotypes, IgD-Fc displays markedly different orientations of the Cdelta3 domains in the Cdelta3 domain dimer and the lowest interface area of all the human isotypes. The nature of the residues that form the dimer interface also differs from those conserved in the other isotypes. By contrast, the interface between the Cdelta2 and Cdelta3 domains in each chain is the largest among the human isotypes. This interface is characterized by two binding pockets, not seen in other isotypes, and points to a potential role for the Cdelta2/Cdelta3 interface in stabilizing the IgD-Fc homodimer. We investigated the thermal stability of IgD-Fc, alone and in the context of an intact IgD antibody, and found that IgD-Fc unfolds in a single transition. Human IgD-Fc clearly has unique structural features not seen in the other human isotypes, and comparison with other mammalian IgD sequences suggests that these unique features might be widely conserved.
-Authors:
+The Crystal Structure of Human IgD-Fc Reveals Unexpected Differences With Other Antibody Isotypes.,Davies AM, Bui TTT, Pacheco-Gomez R, Vester SK, Beavil AJ, Gould HJ, Sutton BJ, McDonnell JM Proteins. 2024 Nov 25. doi: 10.1002/prot.26771. PMID:39582378<ref>PMID:39582378</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9fmb" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Davies AM]]
+[[Category: McDonnell JM]]

9fmb

From Proteopedia

Current revision

Crystal structure of human IgD-Fc

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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