Structural Congruency of Ligand Binding to the Insulin and Insulin/Type 1 Insulin-like Growth Factor Hybrid Receptors
Structural Congruency of Ligand Binding to the Insulin and Insulin/Type 1 Insulin-like Growth Factor Hybrid Receptors
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DOI：
10.1016/j.str.2015.04.016
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发表时间：
2015-07-07
期刊：
影响因子：
5.7
通讯作者：
Lawrence, Michael C.
中科院分区：
文献类型：
--
作者：
Menting, John G.;Lawrence, Callum F.;Lawrence, Michael C.
同型二聚体胰岛素和1型胰岛素样生长因子受体（IR和IGF-1R）具有共同的结构，每个受体都可以结合家族中的所有三种配体：胰岛素和胰岛素样生长因子I和II （IGF-I和IFG-II）。受体单体也组装成异源二聚体，其主要配体结合位点包括一种受体类型的第一个富含亮氨酸的重复结构域（L1）和第二种受体类型的α链c端段（α CT）。我们在此展示了结合到这种混合初级结合位点的IGF-I的晶体结构，以及与IR L1加富含半胱氨酸结构域（IR310.T）结合的IR aCT肽的无配体版本。这些结构在3.0埃分辨率下进行了细化，证明与胰岛素复合物IR310的各自现有结构一致。T和完整的apo-IR外畴。因此，它们在定义受体家族的新出现但稀疏的结构中提供了关键的缺失环节。
The homodimeric insulin and type 1 insulin-like growth factor receptors (IR and IGF-1R) share a common architecture and each can bind all three ligands within the family: insulin and insulin-like growth factors I and II (IGF-I and IFG-II). The receptor monomers also assemble as heterodimers, the primary ligand-binding sites of which each comprise the first leucine-rich repeat domain (L1) of one receptor type and an alpha-chain C-terminal segment (alpha CT) of the second receptor type. We present here crystal structures of IGF-I bound to such a hybrid primary binding site and of a ligand-free version of an IR aCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures, refined at 3.0-angstrom resolution, prove congruent to respective existing structures of insulin-complexed IR310.T and the intact apo-IR ectodomain. As such, they provide key missing links in the emerging, but sparse, repertoire of structures defining the receptor family.