Structural highlights
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.
Publication Abstract from PubMed
We determined the X-ray crystal structure of an immunoglobulin fragment crystallizable (Fc) heterodimer, EW-RVT, at a resolution of 2.5A and found that the designed asymmetric interaction residues located in the heterodimeric CH3 interface favor Fc heterodimer formation. We further generated an inter-CH3 disulfide-bonded heterodimeric Fc variant, EW-RVT(S-S), which exhibited improved heterodimer formation and thermodynamic stability compared with the parent EW-RVT variant. The crystal structure of EW-RVTS-S superimposed very closely with the wild-type Fc structure. Our results provide the detailed structure of heterodimeric Fc scaffolds, which will be useful for the generation of immunoglobulin G (IgG)-like bispecific antibodies.
Crystal structures of immunoglobulin Fc heterodimers reveal the molecular basis for heterodimer formation.,Choi HJ, Seok SH, Kim YJ, Seo MD, Kim YS Mol Immunol. 2015 Jun;65(2):377-83. doi: 10.1016/j.molimm.2015.02.017. Epub 2015 , Mar 2. PMID:25743157[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Choi HJ, Seok SH, Kim YJ, Seo MD, Kim YS. Crystal structures of immunoglobulin Fc heterodimers reveal the molecular basis for heterodimer formation. Mol Immunol. 2015 Jun;65(2):377-83. doi: 10.1016/j.molimm.2015.02.017. Epub 2015 , Mar 2. PMID:25743157 doi:http://dx.doi.org/10.1016/j.molimm.2015.02.017
