3-Dimensional reconstruction of coral insulin and IR using hhblits alignments
The high conservation of known interfaces between insulin and IR gave us high confidence that there really are insulin and IR homologues in pdam and so we created coral homology models using Swiss modeler. There has been an incredible amount of structural data that has come out recently on the IR (McKern et al., 2006; Menting et al., 2013) (Gutmann et al., 2018) (Weis et al., 2018) especially due to the advances in cryoelectron microscopy (Uchikawa et al., 2019). This has allowed us to use the alignments to reconstruct three-dimensional structural homology models for the coral insulin and IR molecules using Swiss-Modeler (see Methods). This is a relatively complex task for IR, given the large size and dimeric configuration of the receptor. The human IR is composed of extracellular (EC or ecto) domain, transmembrane, and cytoplasmic (CP) domains. The IR EC domain consists of a full-length alpha chain and 194 residues of beta-chain including leucine-rich repeat domains (L-L2), a cysteine rich region (CR) and fibronectin type-III domains (FnIII-1-3). The transmembrane (TM) and juxtamembrane (JM) domains are present in the beta-chain and start after the c-terminal of FnIII. The cytoplasmic domain includes tyrosine kinase domain and betaCT domain. Based on our sequence analysis described in the accompanying paper (ref), we identified 6pxv as the structure that showed the highest sequence coverage. This structure was therefore selected for homology modeling, shown in Figure 2 . The amino acid sequences of the corresponding domains in human and in coral are listed in Table 1 .