Fig. 3: Molecular determinants behind binding specificities in the PDZ-PBM interactome.

A PDZome-binding profile of HPV35 E6 PBM. B The affinity-weighted specificity logo of SNTB1 PDZ matches well with HPV35 E6 PBM at positions p0, p-2, p-3 and p-4, which display favorable contacts in the crystal structure of the SNTB1/HPV35 E6 complex. C MAGI1-2 PDZ logo matches with HPV35 E6 PBM at the same positions, but also at p-5 (Arg), exposed to the acidic β2-β3 loop of MAGI1_2 in the MAGI1/HPV35 E6 complex. Accordingly, HPV35 E6 binds stronger to MAGI1-2 than to SNTB1. D PBMome-binding profile of SYNJ2BP PDZ. E RPS6KA1 PBM matches poorly to the logo of SYNJ2BP. Accordingly, RPS6KA1 binds only weakly to SYNJ2BP. The p-3 phosphorylated RPS6KA1 PBM matches better to SYNJ2BP logo, with acidic phospho-Ser at p-3 contacting two residues of SYNJ2BP β2 and β3 strands in the complex. Accordingly, p-3 phosphorylated RPS6KA1 shows increased binding to SYNJ2BP. F HTLV Tax1 PBM sequence matches strongly with SYNJ2BP logo at p0, p-1, p-2, p-3, and p-4. Accordingly, Tax1 is the strongest SYNJ2BP binder in our interactome. In the SYNJ2BP-Tax1 complex, Glu at p-3 of Tax1 engages similar contacts as pSer of RPS6KA1_−3P, while Arg at p-4 provides additional contact to the α2 helix of SYNJ2BP. G Superposition of Tax1 and p-3 phosphorylated RPS6KA1 PBMs bound to SYNJ2BP. The carboxylate-binding loop of SYNJ2BP is shifted in the phosphorylated RPS6KA1-bound complex, most likely related to unfavorable Val → Leu substitution at p0 of RPS6KA1 PBM. H The logo of SNX27 indicates preference for class 1 PBMs (Ser/Thr residue at p-2). MERS E has a class 3 PBM (Glu at p-2) with poor match to SNX27 logo; yet MERS E binds relatively well to SNX27. In the SNX27/MERS E complex Trp at p-1 of MERS E establishes favorable hydrophobic contacts. I Interactomic distance profile of MERS E in the explored PBM space. The closest neighbor of MERS E is ARVCF, a class 1 PBM with Trp at p-1. Source data are provided as a Source Data file. For further details see Supplementary Figs. 2 and 3, Supplementary Table 1 and Supplementary Data 1. All logos were taken from the ProfAff server.