Fig. 5: A multi-pronged interaction between Axin and GSK3.
a Relative peak heights in a BEST-TROSY spectrum of 80 μM 15N-labeled Lip-A3Axin +/−80 μM GSK3β-K85R and corresponding bleach map (underneath), with coloring and labeling as in Fig. 2c; below, sequence of A3Axin (conservation indicated by JackHMMER plot) spanning Axin LIRα (dark gray underlay) and GIR α-helices as predicted by AF2 and AF3; red, minimal Axin GIR visible in crystal structures of the GSK3-Axin complex27,51; light blue, L396 mutated in L > Q (see Fig. 1a); underlined, conserved PRTxR motif; light gray underlay, binding sites for USP7 (PATS, ANDS) or SIAH (VRVEP); see also Fig. 4a (for residue labeling and colors). b, c Surface representations of GSK3 (light gray) forming multi-pronged interactions with Axin as predicted by AF2 and AF3 through GIR (dark gray) as indicated in panels; Axin LIRα (cyan) and intervening PRTxR motif (gold), with P372, R373 and R376 in stick representation; yellow, ATP (visible in co-crystal structure; PDB code 4NM5); yellow asterisks, catalytic site. Zoomed views of (d–g) LIRα-binding grooves and (h–j) catalytic pocket of GSK3 in electrostatic surface representation, interacting with (d–g) LIRα (cyan) or (h–j) PRTxR motif (gold) in stick representation; light green (h) or white (i, j), LRP6 PPPpSP (PDB code 4NM7); white asterisks, priming site; yellow asterisk, catalytic site.
