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4x4m

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Revision as of 07:01, 29 May 2019

Structure of FcgammaRI in complex with Fc reveals the importance of glycan recognition for high affinity IgG binding

Structural highlights

4x4m 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:	, , , , ,
Gene:	IGHG1 (HUMAN), FCGR1A, FCG1, FCGR1, IGFR1 (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.

Function

[FCGR1_HUMAN] High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Fc gamma receptor I (FcgammaRI) contributes to protective immunity against bacterial infections, but exacerbates certain autoimmune diseases. The sole high-affinity IgG receptor, FcgammaRI plays a significant role in immunotherapy. To elucidate the molecular mechanism of its high-affinity IgG binding, we determined the crystal structure of the extracellular domains of human FcgammaRI in complex with the Fc domain of human IgG1. FcgammaRI binds to the Fc in a similar mode as the low-affinity FcgammaRII and FcgammaRIII receptors. In addition to many conserved contacts, FcgammaRI forms additional hydrogen bonds and salt bridges with the lower hinge region of Fc. Unique to the high-affinity receptor-Fc complex, however, is the conformation of the receptor D2 domain FG loop, which enables a charged KHR motif to interact with proximal carbohydrate units of the Fc glycans. Both the length and the charge of the FcgammaRI FG loop are well conserved among mammalian species. Ala and Glu mutations of the FG loop KHR residues showed significant contributions of His-174 and Arg-175 to antibody binding, and the loss of the FG loop-glycan interaction resulted in an approximately 20- to 30-fold decrease in FcgammaRI affinity to all three subclasses of IgGs. Furthermore, deglycosylation of IgG1 resulted in a 40-fold loss in FcgammaRI binding, demonstrating involvement of the receptor FG loop in glycan recognition. These results highlight a unique glycan recognition in FcgammaRI function and open potential therapeutic avenues based on antibody glycan engineering or small molecular glycan mimics to target FcgammaRI for certain autoimmune diseases.

Structure of FcgammaRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding.,Lu J, Chu J, Zou Z, Hamacher NB, Rixon MW, Sun PD Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):833-8. doi: 10.1073/pnas.1418812112., Epub 2015 Jan 5. PMID:25561553^[5]

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

References

↑ van Vugt MJ, Heijnen AF, Capel PJ, Park SY, Ra C, Saito T, Verbeek JS, van de Winkel JG. FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo. Blood. 1996 May 1;87(9):3593-9. PMID:8611682
↑ Ernst LK, Duchemin AM, Miller KL, Anderson CL. Molecular characterization of six variant Fcgamma receptor class I (CD64) transcripts. Mol Immunol. 1998 Oct;35(14-15):943-54. PMID:9881690
↑ van Vugt MJ, Kleijmeer MJ, Keler T, Zeelenberg I, van Dijk MA, Leusen JH, Geuze HJ, van de Winkel JG. The FcgammaRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain. Blood. 1999 Jul 15;94(2):808-17. PMID:10397749
↑ Edberg JC, Yee AM, Rakshit DS, Chang DJ, Gokhale JA, Indik ZK, Schreiber AD, Kimberly RP. The cytoplasmic domain of human FcgammaRIa alters the functional properties of the FcgammaRI.gamma-chain receptor complex. J Biol Chem. 1999 Oct 15;274(42):30328-33. PMID:10514529
↑ Lu J, Chu J, Zou Z, Hamacher NB, Rixon MW, Sun PD. Structure of FcgammaRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding. Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):833-8. doi: 10.1073/pnas.1418812112., Epub 2015 Jan 5. PMID:25561553 doi:http://dx.doi.org/10.1073/pnas.1418812112

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x4m"

Categories: Human | Large Structures | Lu, J | Sun, P D | Immune system

@@ Line 1: / Line 1: @@
 ==Structure of FcgammaRI in complex with Fc reveals the importance of glycan recognition for high affinity IgG binding==
-<StructureSection load='4x4m' size='340' side='right' caption='[[4x4m]], [[Resolution|resolution]] 3.48&Aring;' scene=''>
+<StructureSection load='4x4m' size='340' side='right'caption='[[4x4m]], [[Resolution|resolution]] 3.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x4m]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X4M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x4m]] 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=4X4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X4M 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=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>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></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]), FCGR1A, FCG1, FCGR1, IGFR1 ([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=4x4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x4m OCA], [http://pdbe.org/4x4m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x4m RCSB], [http://www.ebi.ac.uk/pdbsum/4x4m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x4m ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lu, J]]
 [[Category: Sun, P D]]
 [[Category: Immune system]]

4x4m

From Proteopedia

Revision as of 07:01, 29 May 2019

Structure of FcgammaRI in complex with Fc reveals the importance of glycan recognition for high affinity IgG binding

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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