4hix
Crystal structure of a humanised 3D6 Fab bound to amyloid beta peptide
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 PubMedBapineuzumab is a humanized antibody developed by Pfizer and Johnson & Johnson targeting the amyloid (Abeta) plaques that underlie Alzheimer's disease neuropathology. Here we report the crystal structure of a Fab-Abeta peptide complex that reveals Bapineuzumab surprisingly captures Abeta in a monomeric helical conformation at the N-terminus. Microscale thermophoresis suggests that the Fab binds soluble Abeta(1-40) with a K(D) of 89 (+/-9) nM. The structure explains the antibody's exquisite selectivity for particular Abeta species and why it cannot recognize N-terminally modified or truncated Abeta peptides. Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation.,Miles LA, Crespi GA, Doughty L, Parker MW Sci Rep. 2013 Feb 18;3:1302. doi: 10.1038/srep01302. PMID:23416764[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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