![]() These missing regions in the spike stalk were modeled using a hybrid approach ( Materials and Methods). ( B) The modeled structures in the spike neck, HR2, TM domain, CT, and the two connecting linkers are shown. Of these, cryo-EM structures are only available for the spike head, with the missing regions in the structure shown in red. The residue ranges of these domains are provided along with the experimentally identified glycosylation sites marked on top of the domains. ( A) Schematic of the different functional domains of the spike protein, which can be largely divided into the head and stalk domains: N-terminal domain (NTD), RBD, fusion peptide (FP), heptad repeat 1 (HR1), central helix (CH), connecting domain (CD), spike neck, HR2, TM, and cytoplasmic tail (CT). We show that the identified hinge regions are highly conserved in SARS coronaviruses, highlighting their functional importance in enhancing viral infection, and thereby, provide points for discovery of alternative therapeutics against the virus.Ĭoronaviruses glycosylation molecular dynamics spike protein structural dynamics. Furthermore, palmitoylation of the membrane domain amplifies the local curvature that may prime the fusion. The dynamical range of the spike is considerably reduced in its nonglycosylated form, confining the area explored by the spike on the host cell surface. In agreement with cryogenic electron microscopy (cryo-EM), three flexible hinges in the stalk allow for global conformational heterogeneity of spike in the fully glycosylated system mediated by glycan-glycan and glycan-lipid interactions. Multimicrosecond MD simulations of this model, the longest known single trajectory of the full spike, reveal conformational dynamics employed by the protein to explore the surface of the host cell. Combining homology modeling, protein-protein docking, and molecular dynamics (MD) simulations, we have developed a full spike structure in a native membrane. ![]() Construction of the complete, membrane-bound spike model and the description of its dynamics are critical steps in understanding the inner working of this key element of the viral infection by SARS-CoV-2. While anchored in the viral envelope, for effective virulence, the spike needs to maintain structural flexibility to recognize the host cell surface receptors and bind to them, a property that can heavily depend upon the dynamics of the unresolved domains, most prominently the stalk. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein is the prime target for vaccines, diagnostics, and therapeutic antibodies against the virus.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |