4w4n

Crystal structure of human Fc at 1.80 A

spinqualitylabelsall models 4w4n, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4w4n is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: BMA, FUC, GOL, MAN, NAG 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 IGHG1_HUMAN 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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