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 .