Fig. 1: Structure and Ig configuration of SAML and RTK receptors.

a The molecular structures of SAML and RTK extracellular Ig-like regions are shown with wheat and pale green colors, respectively, in cartoon and surface mode, along with a schematic representation of the corresponding full-length receptors anchored in the cell membrane. N- and C-terminal sites are indicated as well as the transmembrane and intracellular regions, which are assigned accordingly. Figure 1a contains images prepared with BioRender. b Display of analogous vertebrate Ig-like receptors configured by an IgV-IgC1 tandem: PD-L2, Programmed Cell Death 1 Ligand 2 (pale-yellow color), CD200, B-lymphocyte antigen (light gray color), Nectin4, Nectin cell adhesion molecule-4 (blue color) and -B7-H6(NCR3LG1), a ligand to Natural cytotoxicity triggering receptor 3 also known as NKp30 or CD337 (salmon color). c The structures of three different Ig-V sets are also shown for structural comparison purposes: Ab-LC-variable, antibody light chain variable region (violet color), Ab-HC-variable, antibody heavy chain variable region (olive color), VNAR, shark variable domain of new antigen receptor (teal color). Pro-Ser-Thr(P/S/T)-rich domain. d Phylogenetic analysis of these invertebrate IgV domains demonstrates clustering with conserved vertebrate IgV domains from the conserved domain database’s Ig superfamily (CDD IgSF), supporting the hypothesis that IgV-type domains were broadly co-opted for immune recognition across diverse evolutionary lineages. e Phylogenetic tree showing the conserved structural features across vertebrate and invertebrate Ig domains, with an emphasis on the evolutionary conservation of these Ig domains: V-set (green), C1-set (red), C2-set (yellow), and I-set (blue) highlight evolutionary divergence. The tree clusters Ig domains into distinct groups based on structural and sequence conservation. f multiple sequence alignment (MSA) showing sequences of immunoglobulin-like (Ig-like) domains from various proteins or species. Amino acid sequences are aligned to highlight conserved regions and motifs. Key features of the image include. Gaps in the alignment (–) indicate insertions or deletions in some sequences relative to others. The MSA provides a visual summary of conserved regions across the sequences, emphasizing key residues and motifs critical for the structure and function of Ig-like domains. g Comparative table showing the distribution and presence of the different Ig domain sets across vertebrates and invertebrates, specifically focused on immune system components or related aspects. The structural features primarily described in this study, i.e., the finding of a novel Early Variable set, and the presence of IgC1 set in invertebrates, are highlighted with color.