(A, B) Superposition of Arc N-lobe or C-lobe (blue and orange, respectively) with HIV capsid C-lobe (PDB ID, 1A43; yellow). The r.m.s.d. in Cα positions for superposition of the N-lobe (excluding residues 207–214) and C-lobe are 2.6 and 2.3 Å, respectively. The TARPγ2 peptide complexed with Arc N-lobe is colored purple. Helix labels in parentheses followed the reference for HIV capsid domain (Pornillos et al., 2009; Pornillos et al., 2011). (C) The sequence alignment for typical species based on their 3D structural superposition with retrotransposon or retrovirus (PDB ID, 1A43, HIV capsid C-lobe; 3G29, Rous Sarcoma Virus). Hs, Homo sapiens, NP_056008.1; Rn, Rattus norvegicus, NP_062234.1; Gga, Gallus gallus, NP_989763.1; Aca, Anolis carolinensis, XP_003223977.1; Xtr, Xenopus (Silurana) tropicalis, XP_002934511.1; Dme, Drosophila melanogaster, Arc1, Q7K1U0; Dr2, Danio rerio, XP_001919627; _N and _C refer to N-lobe and C-lobe, respectively. Secondary structures of Arc N-lobe and HIV C-lobe (PDB 1A43) are shown on the top in red and blue, respectively. Arc C-lobe secondary structure is on the bottom. Residues forming the hydrophobic pocket in Arc N-lobe are marked with a red star above the sequence alignment. The pair of aromatic residues anchoring N-terminal beta strand on alpha helix bundle core is highlighted with yellow solid circles. The numbers in the box indicate three categories (1 = N-lobes, 2 = Virus, 3 = C-lobes). The conservative residues across different species are marked in grey. (D) Domain organization of Arc homologues and several retrotransposons from typical species. Arc N-lobe and C-lobe region are colored blue and orange, respectively. CCHC labels zinc knuckle. Other domains of retrotransposon namely RT (Reverse transcriptase), RH (RNase HI) and INT (Integrase) are shown in pink. (E) The phylogenetic tree inferred based on the concatenated analysis of capsid domains from typical species. Oan, Ornithorhynchus anatinus, XP_001512750.1; Dr1, Danio rerio, XP_005157614; DR3, Danio rerio, XP_005156176.1; Tca1, Tribolium castaneum, XP_001812244; Tca2, Tribolium castaneum, XP_001807351.1; Sbi, Sorghum bicolor, XP_002457951.1; Fr, Fragaria vesca subsp.Vesca, XP_004301673.1.