Fig. 1. Structures of Alpha variant spike interacting with ACE2 receptor.

a Surface representations of predominant molecular species present when ACE2 is mixed with the Alpha variant spike expressed in the presence (left panel) or absence (middle panel) of furin inhibitor I, compared to the predominant species when ACE2 is mixed with the original (Wuhan) spike from our previous study (right panel) (PDB ID 7A91⁵). ACE2 is coloured in green, with monomers of the spike coloured in blue, goldenrod, and rosy brown in the middle panel and rosy brown for S monomers in the right and left panels. b Comparison of the domain movements of S complexed to ACE2 in its trimeric (middle) compared to monomeric (left) form. The monomeric and trimeric ACE2 S1 subunits can be aligned very closely on the ACE2/RBD components but the NTD subdomain (NTD-s, pallid blue) and the NTD (blue) are rotated by 95° and their centre of mass translated by 25 Å in the monomer compared with the trimer, resulting in a conformation incompatible with maintenance of the trimeric state. The furin-cleavage site lies on a loop (shown as dotted line) between the C-terminus of the NTDG and S2 and thus cleavage appears to be able to release sufficient strain to allow the resulting ACE2 complex to remain stable as a trimer. The S1 subunits are shown as surface representation and the S2 core as cartoons. c The ring formed by S1 subunits of the trimer upon binding to three ACE2 molecules (surface representation) remains attached to the exposed S2 core through interactions between the S2′ subunit of one monomer (peach) and NTD-s (pallid blue) and RBD-s (plum) domains of the adjacent one. Domains are coloured: RBD in rosy brown, RBD subdomain (RBD-s) in plum, NTD subdomain (NTD-s) in cyan, NTD in navy, and S2 of the same chain as coloured S1 domains in red.