a comparative structural bioinformatics analysis of the insulin receptor family ectodomain based on phylogenetic information比较结构生物信息学分析胰岛素受体家族的ectodomain基于系统发育信息.pdfVIP

A Comparative Structural Bioinformatics Analysis of the Insulin Receptor Family Ectodomain Based on Phylogenetic Information ´ 1¤ 1 3 1 1,2 Miguel E. Renterıa , Neha S. Gandhi , Pablo Vinuesa , Erik Helmerhorst , Ricardo L. Mancera * 1 Western Australian Biomedical Research Institute and School of Biomedical Sciences, Curtin University of Technology, Perth, Western Austrailia, Australia, 2 School of ´ ´ ´ Pharmacy, Curtin University of Technology, Perth, Western Austrailia, Australia, 3 Centro de Ciencias Genomicas, Universidad Nacional Autonoma de Mexico, Cuernavaca, Morelos, Mexico Abstract The insulin receptor (IR), the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor-related receptor (IRR) are covalently-linked homodimers made up of several structural domains. The molecular mechanism of ligand binding to the ectodomain of these receptors and the resulting activation of their tyrosine kinase domain is still not well understood. We have carried out an amino acid residue conservation analysis in order to reconstruct the phylogeny of the IR Family. We have confirmed the location of ligand binding site 1 of the IGF1R and IR. Importantly, we have also predicted the likely location of the insulin binding site 2 on the surface of the fibronectin type III domains of the IR. An evolutionary conserved surface on the second leucine-rich domain that may interact with the ligand could not be detected. We suggest a possible mechanical trigger of t