Sequential Conformational Changes in the Morbillivirus Attachment Protein Initiate the Membrane Fusion Process

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With the ultimate aim to develop pan-morbillivirus fusion inhibitors, we here characterized a potent neutralizing monoclonal antibody. The antibody recognizes the ectodomain of the membrane-bound tetrameric attachment (H) protein, which together with the fusion protein and a host cell receptor executes plasma membrane fusion to deliver the viral genetic information into the cell. The H-ectodomain consists of a short F-binding/activating stalk region supporting receptor-binding head domains. Molecular characterization of the identified mAb epitope (which locates in the membrane-distal stalk module called “spacer”), enabled us to unravel two sequential conformational changes occurring in CDV H-tetramers that stand at the core of the molecular mechanism translating receptor binding to F-triggering. We additionally propose that both rearrangements are triggered upon receptor-induced “de-activation” of an auto-repressed state assumed by H prior to receptor binding. This locked state enables H/F interaction while preventing premature F-activation. Furthermore, although paramyxovirus attachment proteins may fold into very similar “pre-receptor-bound” conformational states, the presence of the “spacer” module in the stalk emerges as a key determinant leading to distinct mechanisms of membrane fusion triggering.

Vyšlo v časopise: Sequential Conformational Changes in the Morbillivirus Attachment Protein Initiate the Membrane Fusion Process. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004880
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004880

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