4w4o
From Proteopedia
High-resolution crystal structure of Fc bound to its human receptor Fc-gamma-RI
Structural highlights
DiseaseIGHG1_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. FunctionPublication Abstract from PubMedCell-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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