Model of the 3D structure of A. thaliana HAP2 ectodomain indicates it is a class II fusogen. (A) Diagram of A. thaliana HAP2 protein colored by domains according to the ectodomain modeled structure: signal peptide (sp) and transmembrane domain (TM), black; domain I, red; domain II, yellow; domain III, blue; domain I–III linker, cyan; stem, magenta; and intracellular domain, gray. (B) Cartoon of AtHAP2 ectodomain modeled structure (residues 41–494), alongside with C. elegans EFF-1 (PDB 4OJC), dengue virus E glycoprotein (PDB 4GSX), Semliki Forest virus E1 glycoprotein (SFV E1; PDB 1RER), and severe fever with thrombocytopenia syndrome virus glycoprotein Gc (SFTSV Gc; PDB 5G47) class II fusion proteins. Structures are colored according to domains as in A and E; cd loops are shown in orange (facing up). (C) Structural similarity scores between experimental and modeled fusogens computed after flexible structural alignment. Blue matrix: TM-scores (values >0.5 are indicative of significant structural similarity); orange matrix: z-scores (values >2 are considered as indicative of significant structural similarity). (D) Unrooted tree inferred using a distance matrix. Superscript gray M indicates modeled structure; colors are HAP2, blue; EFF-1/AFF-1/FF, green; class II viral fusogens, red (Fig. S3 A). (E) Structure-based alignment of AtHAP2 ectodomain with fusion proteins shown in B. Background colors indicate the domains organization (as in A and B); arrows in color and rounded rectangles denote β sheets and α helices, respectively. The black box in AtHAP2 sequence marks the HAP2/GCS1 domain; the cd loops are marked in orange. Cysteines involved in conserved disulfide bonds stabilizing the cd loop are denoted in bold italics.