Ward Colin W, Lawrence Michael C, Streltsov Victor A, Adams Timothy E, McKern Neil M
Australian Commonwealth Scientific and Research Organization Molecular and Health Technologies, 343 Royal Parade, Parkville, Victoria 3052, Australia.
Trends Biochem Sci. 2007 Mar;32(3):129-37. doi: 10.1016/j.tibs.2007.01.001. Epub 2007 Feb 5.
The insulin receptor (IR) and epidermal growth factor receptor (EGFR; also known as ErbB) families exhibit similarities in the composition of their ectodomains. The past five years have seen structures determined for all members of the EGFR family including some complexes with ligand or monoclonal antibody fragments. These structures have led to a clearer understanding of their mechanism of activation and inhibition. By contrast, obtaining equivalent understanding of the IR family has lagged behind. However, within the past year, structures of partial and complete ectodomains of the IR have been published that show that the extracellular region of the receptor adopts an unexpected 'inverted V' conformation relative to the cell membrane. This is very different from the folded-over (tethered) conformation of the unactivated EGFR and provides insight into the potential mechanism of activation of the IR.
胰岛素受体（IR）家族和表皮生长因子受体（EGFR；也称为ErbB）家族在其胞外结构域的组成上表现出相似性。在过去五年中，已确定了EGFR家族所有成员的结构，包括一些与配体或单克隆抗体片段的复合物结构。这些结构使人们对其激活和抑制机制有了更清晰的认识。相比之下，对IR家族的同等认识则滞后了。然而，在过去一年里，已发表了IR部分和完整胞外结构域的结构，这些结构表明，相对于细胞膜，受体的细胞外区域呈现出意想不到的“倒V”构象。这与未激活的EGFR的折叠（束缚）构象非常不同，并为IR的潜在激活机制提供了见解。
