Fig. 3: Design of highly sensitive and chemotactic receptor–peptide pairs.
From: Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis
a–d Shifts in sensitivity (mean fitted value of dose-response curve fits ± s.e.m., n = 5 for Cdyn:V3Y, n = 4 for Csedy:V3Y-Y7L and Csedy:WT, n = 3 for all other pairs) and maximum activity (fitted value) for various receptor–peptide pairs involving the following designed peptides: a CXCL12 Y7L variant, b CXCL12 V3 substitutions, c CXCL12 V3Y/W-Y7L. d Changes in potency and efficacy across three separate experiments (mean ± s.e.m., n = 3 independent experiments). e Schematic of Boyden chamber migration assay of T cells transduced with engineered receptors and f migratory responses of transduced primary human T cells towards full-length chemokine. Bars are colored according to the transduced CXCR4 variant, and individual points are colored according to the CXCL12 variant (mean ± s.d., n = 3 for WT:V3Y-Y7L, Cdyn:WT, Cdyn:V3Y; mean ± s.d., n = 4 for WT:WT, Csedy:WT, Csedy:V3Y-Y7L; mean ± s.d., n = 5 for WT:V3Y, Csel2:WT; mean ± s.d., n = 6 for Csel2:V3Y-Y7L). Significance shown with two-sided unpaired t-test p values to WT:WT migration. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001 (p = 0.0297 for WT:V3Y, p = 0.0334 for WT:V3Y-Y7L, p = 0.0141 for Csel2:WT, p < 0.0001 for Csedy:WT, p = 0.0205 for Cdyn:WT, p = 0.005 Csel2:V3Y-Y7L, p = 0.0001 for Csedy:V3Y-Y7L, p = 0.0008 for Cdyn:V3Y).
