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• W3204871615 endingPage "2986" @default.
• W3204871615 startingPage "2978" @default.
• W3204871615 abstract "The SARS-CoV-2 spike protein is the primary antigenic determinant of the virus and has been studied extensively, yet the process of membrane fusion remains poorly understood. The fusion domain (FD) of viral glycoproteins is well established as facilitating the initiation of membrane fusion. An improved understanding of the structural plasticity associated with these highly conserved regions aids in our knowledge of the molecular mechanisms that drive viral fusion. Within the spike protein, the FD of SARS-CoV-2 exists immediately following S2′ cleavage at the N-terminus of the S2 domain. Here we have shown that following the introduction of a membrane at pH 7.4, the FD undergoes a transition from a random coil to a more structurally well-defined postfusion state. Furthermore, we have classified the domain into two distinct regions, a fusion peptide (FP, S816–G838) and a fusion loop (FL, D839–F855). The FP forms a helix–turn–helix motif upon association with a membrane, and the favorable entropy gained during this transition from a random coil is likely the driving force behind membrane insertion. Membrane depth experiments then revealed the FP is found inserted within the membrane below the lipid headgroups, while the interaction of the FL with the membrane is shallower in nature. Thus, we propose a structural model relevant to fusion at the plasma membrane in which the FP inserts itself just below the phospholipid headgroups and the FL lays upon the lipid membrane surface." @default.
• W3204871615 created "2021-10-11" @default.
• W3204871615 creator A5048266623 @default.
• W3204871615 creator A5091361972 @default.
• W3204871615 date "2021-09-27" @default.
• W3204871615 modified "2023-09-30" @default.
• W3204871615 title "Identifying Distinct Structural Features of the SARS-CoV-2 Spike Protein Fusion Domain Essential for Membrane Interaction" @default.
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• W3204871615 doi "https://doi.org/10.1021/acs.biochem.1c00543" @default.
• W3204871615 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8491435" @default.
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• W3204871615 hasPublicationYear "2021" @default.
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