Insulin receptor (IR) and epidermal growth factor receptors (EGFR) are members of the receptor tyrosine kinase super family. The extracellular regions of both IR and EGFR contain two L domains. Many crystal structures of the extracellular regions of the IR and EGFR families have been determined in both the unliganded state and in complexes with ligands. The structures reveal that the L domains consist of four to six leucine rich repeats (LRRs); although, their amino acid sequences are highly variable. The present bioinformatic analysis reveals some features on the LRRs and the structures. We conclude that the LRRs in the L domains belong to a non-canonical motif differing from the known (canonical) motifs; the repeat units consist of two β-strands and the overall shape of the LRRs resembles a prism. To characterize the spatial arrangement of the two L-domains we propose two parameters; the distance between the two L domains (D) and the angle between the two axes showing the direction of the β-sheet stacking of the LRRs in the L domains (Ψ). These two parameters, D and Ψ, describe an essential feature of the structures and ligand induced structural changes.
Author(s): Hiroki Miyashita, Robert H. Kretsinger, and Norio Matsushima