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5d4q

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Revision as of 12:30, 6 November 2017

Crystal structure of GASDALIE IgG1 Fc

Structural highlights

5d4q is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Gene:	IGHG1 (HUMAN)
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.

Publication Abstract from PubMed

The Fc region of Immunoglobulin G (IgG) initiates inflammatory responses such as antibody-dependent cell-mediated cytotoxicity (ADCC) through binding to activating Fc receptors (FcgammaRI, FcgammaRIIa, FcgammaRIIIa). These receptors are expressed on the surface of immune cells including macrophages, dendritic cells, and natural killer cells. An inhibitory receptor, FcgammaRIIb, is expressed on macrophages and other myeloid leukocytes simultaneously with the activating receptor FcgammaRIIa, thereby setting a threshold for cell activation. The affinity of IgG Fc for binding activating Fc receptors depends on IgG subclass and the composition of N-linked glycans attached to a conserved asparagine in the Fc CH2 domain. For example, Fc regions with afucosylated glycans bind more tightly to FcgammaRIIIa than fucosylated Fc, and afucosylated Fcs exhibit enhanced ADCC activity in vivo and in vitro. Enhanced pro-inflammatory responses have also been seen for Fc regions with amino acid substitutions. GASDALIE Fc is an Fc mutant (G236A/S239D/A330L/I332E) that exhibits a higher affinity for FcgammaRIIIa and increased effector functions in vivo compared to wild-type Fc. To explore its altered functions, we compared the affinities of GASDALIE and wild-type Fc for activating and inhibitory FcgammaRs. We also determined the crystal structure of GASDALIE Fc alone and bound to FcgammaRIIIa. The overall structure of GASDALIE Fc alone was similar to wild-type Fc structures, however, increased electrostatic interactions in the GASDALIE Fc:FcgammaRIIIa interface compared with other Fc:FcgammaR structures suggest a mechanism for the increased affinity of GASDALIE Fc for FcgammaRIIIa.

Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcgammaRIIIa.,Ahmed AA, Keremane SR, Vielmetter J, Bjorkman PJ J Struct Biol. 2016 Apr;194(1):78-89. doi: 10.1016/j.jsb.2016.02.001. Epub 2016, Feb 2. PMID:26850169^[1]

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

References

↑ Ahmed AA, Keremane SR, Vielmetter J, Bjorkman PJ. Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcgammaRIIIa. J Struct Biol. 2016 Apr;194(1):78-89. doi: 10.1016/j.jsb.2016.02.001. Epub 2016, Feb 2. PMID:26850169 doi:http://dx.doi.org/10.1016/j.jsb.2016.02.001

1 Structural highlights
2 Disease
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/5d4q"

@@ Line 3: / Line 3: @@
 <StructureSection load='5d4q' size='340' side='right' caption='[[5d4q]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5d4q]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D4Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D4Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5d4q]] is a 2 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=5D4Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D4Q 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=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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5d4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d4q OCA], [http://pdbe.org/5d4q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d4q RCSB], [http://www.ebi.ac.uk/pdbsum/5d4q PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5d4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d4q OCA], [http://pdbe.org/5d4q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d4q RCSB], [http://www.ebi.ac.uk/pdbsum/5d4q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d4q ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Ahmed, A A]]
 [[Category: Bjorkman, P J]]

5d4q

From Proteopedia

Revision as of 12:30, 6 November 2017

Crystal structure of GASDALIE IgG1 Fc

Structural highlights

Disease

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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