Forbes Briony E
School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia 5005, Australia.
Pediatr Endocrinol Rev. 2011 Jun;8(4):374-81.
Insulin-like growth factors (IGFs) act via the Type 1 IGF receptor (IGF-1R) to promote growth and development. Recent structural and site-directed mutagenesis studies have provided detailed insight into the mechanism of interaction between the IGFs and the IGF-IR. Studies of the insulin: insulin receptor interaction have provided important additional understanding of the mechanisms underlying the IGF:IGF-1R interaction. The recent crystal structure of the insulin receptor ectodomain showed a folded over conformation accommodating two potential ligand binding pockets. The ligand interacts with the receptor at two different sites within a binding pocket to achieve high affinity binding and activation of the receptor. In this review the effect of mutations in the human IGF1 and IGF-1R genes so for reported are explained in terms of the effect on ligand binding and receptor activation. The severity of patient phenotype can generally be correlated to the effect of the mutation on protein structure and function.
胰岛素样生长因子（IGFs）通过1型IGF受体（IGF-1R）发挥作用，以促进生长和发育。最近的结构和定点诱变研究对IGFs与IGF-IR之间的相互作用机制提供了详细的见解。胰岛素与胰岛素受体相互作用的研究为理解IGF与IGF-1R相互作用的潜在机制提供了重要的补充。胰岛素受体胞外域的最新晶体结构显示出一种折叠构象，可容纳两个潜在的配体结合口袋。配体在结合口袋内的两个不同位点与受体相互作用，以实现高亲和力结合和受体激活。在这篇综述中，根据对配体结合和受体激活的影响，解释了迄今为止报道的人类IGF1和IGF-1R基因突变的作用。患者表型的严重程度通常与突变对蛋白质结构和功能的影响相关。
