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Crystal Structure of Motavizumab Fab Bound to Peptide EpitopeCrystal Structure of Motavizumab Fab Bound to Peptide Epitope
Structural highlights
FunctionFUS_HRSVA Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMotavizumab is approximately tenfold more potent than its predecessor, palivizumab (Synagis), the FDA-approved monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection. The structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the RSV fusion (F) glycoprotein reveals the structural basis for this greater potency. Modeling suggests that motavizumab recognizes a different quaternary configuration of the F glycoprotein than that observed in a homologous structure. Structural basis of respiratory syncytial virus neutralization by motavizumab.,McLellan JS, Chen M, Kim A, Yang Y, Graham BS, Kwong PD Nat Struct Mol Biol. 2010 Feb;17(2):248-50. Epub 2010 Jan 24. PMID:20098425[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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