Structural highlights
4ku1 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.
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| Method: | X-ray diffraction, Resolution 1.9Å |
| Ligands: | , , , , , |
| 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
The fragment crystallizable (Fc) region links the key pathogen identification and destruction properties of immunoglobulin G (IgG). Pathogen opsonization positions Fcs to activate pro-inflammatory Fcgamma receptors (FcgammaRs) on immune cells. The cellular response and committal to a damaging, though protective, immune response are tightly controlled at multiple levels. Control mechanisms are diverse and in many cases unclear, but one frequently suggested contribution originates in FcgammaR affinity being modulated through shifts in Fc conformational sampling. Here, we report a previously unseen IgG1 Fc conformation. This observation motivated an extensive molecular dynamics investigation of polypeptide and glycan motions that revealed greater amplitude of motion for the N-terminal Cgamma2 domains and N-glycan than previously observed. Residues in the Cgamma2/Cgamma3 interface and disulfide-bonded hinge were identified as influencing the Cgamma2 motion. Our results are consistent with a model of Fc that is structurally dynamic. Conformational states that are competent to bind immune-stimulating FcgammaRs interconverted with Fc conformations distinct from those observed in FcgammaR complexes, which may represent a transient, nonbinding population.
Immunoglobulin G1 Fc Domain Motions: Implications for Fc Engineering.,Frank M, Walker RC, Lanzilotta WN, Prestegard JH, Barb AW J Mol Biol. 2014 Feb 9. pii: S0022-2836(14)00069-2. doi:, 10.1016/j.jmb.2014.01.011. PMID:24522230[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Frank M, Walker RC, Lanzilotta WN, Prestegard JH, Barb AW. Immunoglobulin G1 Fc Domain Motions: Implications for Fc Engineering. J Mol Biol. 2014 Feb 9. pii: S0022-2836(14)00069-2. doi:, 10.1016/j.jmb.2014.01.011. PMID:24522230 doi:http://dx.doi.org/10.1016/j.jmb.2014.01.011
