1t89
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Fcgamma receptors mediate antibody-dependent inflammatory responses and | + | Fcgamma receptors mediate antibody-dependent inflammatory responses and cytotoxicity as well as certain autoimmune dysfunctions. Here we report the crystal structure of a human Fc receptor (FcgammaRIIIB) in complex with an Fc fragment of human IgG1 determined from orthorhombic and hexagonal crystal forms at 3.0- and 3.5-A resolution, respectively. The refined structures from the two crystal forms are nearly identical with no significant discrepancies between the coordinates. Regions of the C-terminal domain of FcgammaRIII, including the BC, C'E, FG loops, and the C' beta-strand, bind asymmetrically to the lower hinge region, residues Leu(234)-Pro(238), of both Fc chains creating a 1:1 receptor-ligand stoichiometry. Minor conformational changes are observed in both the receptor and Fc upon complex formation. Hydrophobic residues, hydrogen bonds, and salt bridges are distributed throughout the receptor.Fc interface. Sequence comparisons of the receptor-ligand interface residues suggest a conserved binding mode common to all members of immunoglobulin-like Fc receptors. Structural comparison between FcgammaRIII.Fc and FcepsilonRI.Fc complexes highlights the differences in ligand recognition between the high and low affinity receptors. Although not in direct contact with the receptor, the carbohydrate attached to the conserved glycosylation residue Asn(297) on Fc may stabilize the conformation of the receptor-binding epitope on Fc. An antibody-FcgammaRIII model suggests two possible ligand-induced receptor aggregations. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Lupus erythematosus, systemic, susceptibility OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146740 146740]], Neutropenia, alloimmune neonatal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146740 146740]], Viral infections, recurrent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146740 146740]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1T89 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure | + | 1T89 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1IIX. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T89 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Fridman, W | + | [[Category: Fridman, W H.]] |
[[Category: Motyka, S.]] | [[Category: Motyka, S.]] | ||
[[Category: Radaev, S.]] | [[Category: Radaev, S.]] | ||
[[Category: Sautes-Fridman, C.]] | [[Category: Sautes-Fridman, C.]] | ||
| - | [[Category: Sun, P | + | [[Category: Sun, P D.]] |
[[Category: cd16]] | [[Category: cd16]] | ||
[[Category: fc gamma receptor]] | [[Category: fc gamma receptor]] | ||
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[[Category: immunoglobulin]] | [[Category: immunoglobulin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:54 2008'' |
Revision as of 13:10, 21 February 2008
|
CRYSTAL STRUCTURE OF A HUMAN TYPE III FC GAMMA RECEPTOR IN COMPLEX WITH AN FC FRAGMENT OF IGG1 (HEXAGONAL)
Contents |
Overview
Fcgamma receptors mediate antibody-dependent inflammatory responses and cytotoxicity as well as certain autoimmune dysfunctions. Here we report the crystal structure of a human Fc receptor (FcgammaRIIIB) in complex with an Fc fragment of human IgG1 determined from orthorhombic and hexagonal crystal forms at 3.0- and 3.5-A resolution, respectively. The refined structures from the two crystal forms are nearly identical with no significant discrepancies between the coordinates. Regions of the C-terminal domain of FcgammaRIII, including the BC, C'E, FG loops, and the C' beta-strand, bind asymmetrically to the lower hinge region, residues Leu(234)-Pro(238), of both Fc chains creating a 1:1 receptor-ligand stoichiometry. Minor conformational changes are observed in both the receptor and Fc upon complex formation. Hydrophobic residues, hydrogen bonds, and salt bridges are distributed throughout the receptor.Fc interface. Sequence comparisons of the receptor-ligand interface residues suggest a conserved binding mode common to all members of immunoglobulin-like Fc receptors. Structural comparison between FcgammaRIII.Fc and FcepsilonRI.Fc complexes highlights the differences in ligand recognition between the high and low affinity receptors. Although not in direct contact with the receptor, the carbohydrate attached to the conserved glycosylation residue Asn(297) on Fc may stabilize the conformation of the receptor-binding epitope on Fc. An antibody-FcgammaRIII model suggests two possible ligand-induced receptor aggregations.
Disease
Known diseases associated with this structure: Lupus erythematosus, systemic, susceptibility OMIM:[146740], Neutropenia, alloimmune neonatal OMIM:[146740], Viral infections, recurrent OMIM:[146740]
About this Structure
1T89 is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entry 1IIX. Full crystallographic information is available from OCA.
Reference
The structure of a human type III Fcgamma receptor in complex with Fc., Radaev S, Motyka S, Fridman WH, Sautes-Fridman C, Sun PD, J Biol Chem. 2001 May 11;276(19):16469-77. Epub 2001 Jan 31. PMID:11297532
Page seeded by OCA on Thu Feb 21 15:10:54 2008
