Fig. 9
Structure models of human CXCL10(1–77). A Structure models of human CXCL10(1–77) of AlfaFold DB (right; AF-P02778-F1 without signal sequence). This model is based on the crystal structure of CXCL10 in hexagonal (H) form [PDB accession code 1O80], crystal structure of CXCL10 in monoclinic (M) form [PDB accession code 1O7Y], crystal structure of CXCL10 in tetragonal (T) form [PDB accession code 1O7Z], and NMR spectroscopy-determined CXCL10 [PDB accession code 1LV9] [45, 46] whereby unobserved Ser76 and Pro77 were predicted through AlfaFold DB. Secondary structures of human CXCL10(1–77) are displayed. CXCL10 has an N/20s loop (green), three antiparallel β-sheets (cyan), 30s loop (yellow), 40s loop (blue), and an α-helix (red). The inset shows human CXCL10(1–77) (AF-P02778-F1; left) and murine CXCL10(1–77) of AlfaFold DB (AF-Q3UK71-F1 without signal sequence; right). Conserved residues in mCXCL10(1–77) and human CXCL10(1–77) (magenta) and residues that are not conserved (grey) are displayed. B The structural model of human CXCL10(1–77) of AlfaFold DB (AF-P02778-F1) is shown from two different perspectives with a transparent surface to visualize amino acid side chains. The four C-terminal residues that are shedded in CXCL10(1–73) (cyan) are located in close proximity to predicted potential GAG-binding residues Arg22, Lys46, Lys47, Lys48, Lys62, and Lys66 (red) [46]. C The structural model of human CXCL10(1–77) of AlfaFold DB (AF-P02778-F1) is displayed from two different perspectives with a non-transparent surface to visualize the receptor interaction surface. Potential CXCR3 binding residues of CXCL10 are indicated in different colors as previously shown by Swaminathan et al. [46]: residues of human CXCL10(1–77) found to be perturbed in 2D 15N-1H HSQC NMR spectra by the addition of an N-terminal CXCR3 peptide CXCR3(22–42) [45] (Val7, Arg8, Gln17, Val19, Gln34 and Arg38; magenta), residues bound by a CXCR3-blocking anti-CXCL10 monoclonal antibodies preventing chemotaxis and calcium mobilization [46] (Asn20-Cys36; green), and residues aligned to the CXCL8 binding region to CXCR1 (Arg8-Pro21 and Glu40-Gly49; yellow) [77]. The four C-terminal residues that are shedded in CXCL10(1–73) (cyan) are positioned in vicinity of several potential CXCR3 binding residues