|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Wild type Fc (wtFc)== | | ==Wild type Fc (wtFc)== |
| - | <StructureSection load='4q7d' size='340' side='right' caption='[[4q7d]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='4q7d' size='340' side='right'caption='[[4q7d]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4q7d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q7D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q7D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4q7d]] 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=4Q7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q7D 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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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]] 2.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4q74|4q74]], [[4q6y|4q6y]]</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=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=4q7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q7d OCA], [http://pdbe.org/4q7d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q7d RCSB], [http://www.ebi.ac.uk/pdbsum/4q7d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q7d 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=4q7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q7d OCA], [https://pdbe.org/4q7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q7d RCSB], [https://www.ebi.ac.uk/pdbsum/4q7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q7d ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[http://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. | + | [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] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ahmed, A A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bjorkman, P J]] | + | [[Category: Large Structures]] |
| - | [[Category: Giddens, J]] | + | [[Category: Ahmed AA]] |
| - | [[Category: Lomino, J V]] | + | [[Category: Bjorkman PJ]] |
| - | [[Category: Pincetic, A]] | + | [[Category: Giddens J]] |
| - | [[Category: Ravetch, J V]] | + | [[Category: Lomino JV]] |
| - | [[Category: Wang, L X]] | + | [[Category: Pincetic A]] |
| - | [[Category: Immune system]] | + | [[Category: Ravetch JV]] |
| - | [[Category: Immunoglobulin fold]] | + | [[Category: Wang LX]] |
| Structural highlights
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
Publication Abstract from PubMed
Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of Intravenous Immunoglobulin G (IVIG) requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of IVIG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal alpha2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully di-sialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro- to anti-inflammatory activity of the Fc.
Structural characterization of anti-inflammatory Immunoglobulin G Fc proteins.,Ahmed AA, Giddens J, Pincetic A, Lomino JV, Ravetch JV, Wang LX, Bjorkman PJ J Mol Biol. 2014 Jul 15. pii: S0022-2836(14)00340-4. doi:, 10.1016/j.jmb.2014.07.006. PMID:25036289[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ahmed AA, Giddens J, Pincetic A, Lomino JV, Ravetch JV, Wang LX, Bjorkman PJ. Structural characterization of anti-inflammatory Immunoglobulin G Fc proteins. J Mol Biol. 2014 Jul 15. pii: S0022-2836(14)00340-4. doi:, 10.1016/j.jmb.2014.07.006. PMID:25036289 doi:http://dx.doi.org/10.1016/j.jmb.2014.07.006
|
