Tracking the opening of spike crowns on the surface of coronaviruses

Circulating over years after the pandemic, SARS-CoV-2 still poses a threat to the human society. The onset of viral infection requires the opening of a trimeric protein, called spike, located on the viral surface essential for binding the host-cell receptors and the subsequent fusion into the host cells. Upon spike-crown opening, one to three Receptor Binding Domains (RBD) rise from the compactly assembled spike head, reaching for the host receptors. Many spike structures were solved that captured RBDs in the different down-to-up trimeric states. These structures not only depict spikes conformational change but also help design the more efficacious antiviral therapeutics. However, such a dynamic crown-opening pathway is hardly described by only few stationary pictures, and questions yet remain. Do all RBDs rise following the same track in the various studies? If they do, what does this track look like? Is there a common adaptive conformational change of spike as its crown opens? Do all trimeric RBDs rise cooperatively in each spike? And how does it relate to the antibody-binding event? Here, a general RBD-rising pathway, describing the crown-opening dynamics using two angular parameters, was proposed based on analyzing the published spike structures. These analyses describe not only the orientational change of individual RBDs, but also the asymmetric rising preference of the trimeric RBDs in a single-spike entity. In addition, the quantified map clearly describes RBDs spatial change upon antibody binding, which is often accompanied by an enlarged crown-opening scale. These findings may provide additional clues to develop therapeutics targeting viral spikes in the future. HighlightsO_LI778 spike structures were analyzed that revealed a general RBD-rising pathway. C_LIO_LIMore intermediate-state RBD structures were identified, one of which might be related to the high FRET-signal state. C_LIO_LIRBD twisted upon rotating up. C_LIO_LIAntibodies elicited larger RBD-rising scales. C_LI In summary and {beta} rotation-parameters were introduced that outlined a general RBD-rising pathway, along which the DOWN-, intermediate-, and UP-state RBDs were easily detected and compared that helped explain unresolved issues and provided additional clues in developing therapeutics targeting viral spikes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/686173v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@10a0be9org.highwire.dtl.DTLVardef@941aa3org.highwire.dtl.DTLVardef@160eeb6org.highwire.dtl.DTLVardef@d81356_HPS_FORMAT_FIGEXP M_FIG C_FIG