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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1h3v]] is a 2 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=1H3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H3V FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1h3v]] is a 2 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=1H3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H3V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1h3u|1h3u]], [[1h3t|1h3t]], [[1h3w|1h3w]], [[1h3x|1h3x]], [[1h3y|1h3y]], [[1aj7|1aj7]], [[1d5b|1d5b]], [[1d5i|1d5i]], [[1d6v|1d6v]], [[1dn2|1dn2]], [[1e4k|1e4k]], [[1fc1|1fc1]], [[1fc2|1fc2]], [[1fcc|1fcc]], [[1hzh|1hzh]], [[1i7z|1i7z]], [[1iis|1iis]], [[1iix|1iix]], [[2rcs|2rcs]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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></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=1h3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h3v OCA], [https://pdbe.org/1h3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h3v RCSB], [https://www.ebi.ac.uk/pdbsum/1h3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h3v ProSAT]</span></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=1h3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h3v OCA], [https://pdbe.org/1h3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h3v RCSB], [https://www.ebi.ac.uk/pdbsum/1h3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h3v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 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. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Huber, R]] | + | [[Category: Huber R]] |
| - | [[Category: Jefferis, R]] | + | [[Category: Jefferis R]] |
| - | [[Category: Krapp, S]] | + | [[Category: Krapp S]] |
| - | [[Category: Mimura, Y]] | + | [[Category: Mimura Y]] |
| - | [[Category: Sondermann, P]] | + | [[Category: Sondermann P]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Effector function]]
| + | |
| - | [[Category: Fc-fragment]]
| + | |
| - | [[Category: Fcgr]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin/fc-fragment]]
| + | |
| Structural highlights
1h3v is a 2 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 3.1Å |
| Ligands: | , , , , |
| 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.
Function
IGHG1_HUMAN
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
Antibodies may be viewed as adaptor molecules that provide a link between humoral and cellular defence mechanisms. Thus, when antigen-specific IgG antibodies form antigen/antibody immune complexes the effectively aggregated IgG can activate a wide range of effector systems. Multiple effector mechanisms result from cellular activation mediated through a family of IgG-Fc receptors differentially expressed on leucocytes. It is established that glycosylation of IgG-Fc is essential for recognition and activation of these ligands. IgG antibodies predominate in human serum and most therapeutic antibodies are of the IgG class.The IgG-Fc is a homodimer of N-linked glycopeptide chains comprised of two immunoglobulin domains (Cgamma2, Cgamma3) that dimerise via inter-heavy chain disulphide bridges at the N-terminal region and non-covalent interactions between the C-terminal Cgamma3 domains. The overall shape of the IgG-Fc is similar to that of a "horseshoe" with a majority of the internal space filled by the oligosaccharide chains, only attached through asparagine residues 297.To investigate the influence of individual sugar (monosaccharide) residues of the oligosaccharide on the structure and function of IgG-Fc we have compared the structure of "wild-type" glycosylated IgG1-Fc with that of four glycoforms bearing consecutively truncated oligosaccharides. Removal of terminal N-acetylglucosamine as well as mannose sugar residues resulted in the largest conformational changes in both the oligosaccharide and in the polypeptide loop containing the N-glycosylation site. The observed conformational changes in the Cgamma2 domain affect the interface between IgG-Fc fragments and FcgammaRs. Furthermore, we observed that the removal of sugar residues permits the mutual approach of Cgamma2 domains resulting in the generation of a "closed" conformation; in contrast to the "open" conformation which was observed for the fully galactosylated IgG-Fc, which may be optimal for FcgammaR binding. These data provide a structural rationale for the previously observed modulation of effector activities reported for this series of proteins.
Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity.,Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P J Mol Biol. 2003 Jan 31;325(5):979-89. PMID:12527303[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol. 2003 Jan 31;325(5):979-89. PMID:12527303
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