The relationship between the L1 and L2 domains of the insulin and epidermal growth factor receptors and leucine-rich repeat modules.
BACKGROUND
Leucine-rich repeats are one of the more common modules found in proteins. The leucine-rich repeat consensus motif is LxxLxLxxNxLxxLxxLxxLxx- where the first 11-12 residues are highly conserved and the remainder of the repeat can vary in size Leucine-rich repeat proteins have been subdivided into seven subfamilies, none of which include members of the epidermal growth factor receptor or insulin receptor families despite the similarity between the 3D structure of the L domains of the type I insulin-like growth factor receptor and some leucine-rich repeat proteins.


RESULTS
Here we have used profile searches and multiple sequence alignments to identify the repeat motif Ixx-LxIxx-Nx-Lxx-Lxx-Lxx-Lxx- in the L1 and L2 domains of the insulin receptor and epidermal growth factor receptors. These analyses were aided by reference to the known three dimensional structures of the insulin-like growth factor type I receptor L domains and two members of the leucine rich repeat family, porcine ribonuclease inhibitor and internalin 1B. Pectate lyase, another beta helix protein, can also be seen to contain the sequence motif and much of the structural features characteristic of leucine-rich repeat proteins, despite the existence of major insertions in some of its repeats.


CONCLUSIONS
Multiple sequence alignments and comparisons of the 3D structures has shown that right-handed beta helix proteins such as pectate lyase and the L domains of members of the insulin receptor and epidermal growth factor receptor families, are members of the leucine-rich repeat superfamily.
Ward
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CW
CSIRO Health Sciences and Nutrition, 343 Royal Parade Parkville, Victoria 3052, Australia. Colin.Ward@hsn.csiro.au
Garrett
T P
TP
D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins / Q000737:chemistry; D002417:Cattle; D002645:Chickens; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D011972:Receptor, Insulin / Q000737:chemistry*; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment / Q000379:methods; D014633:Valine / Q000378:metabolism
D029681:Arabidopsis Proteins; D007532:Isoleucine; D010649:Phenylalanine; D066246:ErbB Receptors; D011972:Receptor, Insulin; D007930:Leucine; D014633:Valine