| Structural highlights
4w4o is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , , |
| Related: | 4w4n |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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
Cell-surface Fcgamma receptors mediate innate and adaptive immune responses. Human Fcgamma receptor I (hFcgammaRI) binds IgGs with high affinity and is the only Fcgamma receptor that can effectively capture monomeric IgGs. However, the molecular basis of hFcgammaRI's interaction with Fc has not been determined, limiting our understanding of this major immune receptor. Here we report the crystal structure of a complex between hFcgammaRI and human Fc, at 1.80 A resolution, revealing an unique hydrophobic pocket at the surface of hFcgammaRI perfectly suited for residue Leu235 of Fc, which explains the high affinity of this complex. Structural, kinetic and thermodynamic data demonstrate that the binding mechanism is governed by a combination of non-covalent interactions, bridging water molecules and the dynamic features of Fc. In addition, the hinge region of hFcgammaRI-bound Fc adopts a straight conformation, potentially orienting the Fab moiety. These findings will stimulate the development of novel therapeutic strategies involving hFcgammaRI.
Structural basis for binding of human IgG1 to its high-affinity human receptor FcgammaRI.,Kiyoshi M, Caaveiro JM, Kawai T, Tashiro S, Ide T, Asaoka Y, Hatayama K, Tsumoto K Nat Commun. 2015 Apr 30;6:6866. doi: 10.1038/ncomms7866. PMID:25925696[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
- ↑ Kiyoshi M, Caaveiro JM, Kawai T, Tashiro S, Ide T, Asaoka Y, Hatayama K, Tsumoto K. Structural basis for binding of human IgG1 to its high-affinity human receptor FcgammaRI. Nat Commun. 2015 Apr 30;6:6866. doi: 10.1038/ncomms7866. PMID:25925696 doi:http://dx.doi.org/10.1038/ncomms7866
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