Conformations of cov2-spikes

(A lot of structural data has to be downloaded, be patient until you see a picture)

A vaccination strategy has to have a clear objective, with covid-19 it should be the spike protein. In the course of the infection process the spike protein changes its structure: after docking to the receptor ACE2 the protein is cleaved. This is neccessary for the virus, as only the part remaining in the viral membrane works to the unification of viral and host cell membranes. The (red) is on the surface of the spike proteins and is cut by a protease provided by the host (e. g. homo sapiens). A viral protease wouldn't do, because it is not produced up to this stage. The consequence: the human protease can't know whether the virus is already docked to the receptor, it will cleave also (partly) when the infection mechanism has not started yet. So on the viral surface are also spike fragments (named S2). To recognize structural changes in the spikes after cleavage, we have to observe the inner (secondary) structure . The cut-off part (S1) diffuses away and is now without further interest . The part remaining bound to the virus (S2) is folded into a different shape to induce the membrane fusion. To recognize the refolding process, we colour the spikes not according to protein chain, but according to later function . From the beginnin to the end of the spike protein chains segments are coloured blue, yellow, orange and green. The authors of the study discuss the engagement of the different segments in the refolding mechanism, but visible is only the final result. This is remarkable . The inner structure consisting of very long helices lends a rigidity which makes the S2 stand streight away from the surface. Now back to the spacefilling view and the single strand colour scheme with the glycosylation made visible , we have the fragment in full size. For comparison the whole spike trimer .
What's all this about vaccination?
To the right there is a schematic picture (from the authors of this study) showing the spike variants on the surface of the virus. Our immune system recognizes both forms worth to fight against, maybe the furter protruding parts even better. Other viruses (HIV or RSV which causes respiratory illness in small children) have a similar strategy with their spike proteins. The narrow S2 structures decorated in regular distances by glycosylation do provoke antibodies (like complete spikes), but fatally these are not neutralizing. The immune system is diverted by the production of useless antibodies! These facts have to be evaluated in the development of vaccines, else the immunisation is partly in vain.

this demonstration.

Literature:
Y Cai et al, Science 369, 1586-1592 (2020), DOI 10.1126/science.abd4251