Fig. 2: Clientized S binds to a basic cluster on the coatomer WD40 domain.
From: A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs
A–C Co-crystal structures of SARS-CoV-2 S tail heptapeptides (residues 1267-1273) in complex with β‘WD40. A Thr1273 in wild-type S shows no side-chain interactions with the basic cluster. B Glu1273 in clientized S forms complementary electrostatic interactions with the β‘WD40 basic cluster. C The β‘WD40 surface provides electrostatic complementarity to the S dibasic motif and the C-terminus. Color code: red, acidic; blue, basic. D, E BLI assays show that αWD40 Arg13Ala mutant has weaker affinity for D wild-type S heptapeptide than for, E Thr1273Glu clientized S heptapeptide. F Superposition of wild-type (white) and Arg13Ala mutant (yellow) crystal structures shows minimal perturbation near the mutation site. G, H BLI assays show that αWD40 Arg300Ala mutant has similar affinity for, G wild-type S heptapeptide and, H Thr1273Glu clientized S heptapeptide. I Superposition of wild-type (white) and Arg300Ala mutant (yellow) crystal structures shows minimal perturbation near the mutation site. J, K BLI assays show that αWD40 Lys15Ala mutant shows no interaction with,(J wild-type S heptapeptide or, K Thr1273Glu clientized S heptapeptide. L Superposition of wild-type (white) and Lys15Ala mutant (yellow) crystal structures shows substantial perturbation and inward rotation of Arg13 and His31 side chains in the mutant to block the S heptapeptide binding site. M, N BLI assays for αWD40 shows loss of binding with, M amidated wild-type S heptapeptide but not, N amidated Thr1273Glu clientized S heptapeptide. Color key indicates αWD40 concentrations for BLI assays.
