High-resolution X-ray crystal structures determined in the past six years dramatically influence our view of ligand-induced activation of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Ligand binding to the extracellular region of EGFR promotes a major domain reorganization, plus local conformational changes, that are required to generate an entirely receptor-mediated dimer. In this activated complex the intracellular kinase domains associate to form an asymmetric dimer that supports the allosteric activation of one kinase. These models are discussed with emphasis on recent studies that add details or bolster the generality of this view of activation of this family of receptors. The EGFR family is implicated in several disease states, perhaps most notably in cancers. Activating tumor mutations have been identified in the intracellular and extracellular regions of EGFR. The impact of these tumor mutations on the understanding of EGFR activation and of its inhibition is discussed.

中文翻译：

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表皮生长因子受体调节的基于结构的观点。

在过去六年中确定的高分辨率 X 射线晶体结构极大地影响了我们对配体诱导的表皮生长因子受体 (EGFR) 受体酪氨酸激酶家族激活的看法。配体与 EGFR 细胞外区域的结合促进了主要的结构域重组，以及产生完全受体介导的二聚体所需的局部构象变化。在这种激活的复合物中，细胞内激酶结构域结合形成不对称二聚体，支持一种激酶的变构激活。这些模型的讨论重点是最近的研究，这些研究增加了细节或加强了这一受体家族激活观点的普遍性。EGFR 家族与多种疾病状态有关，可能最显着的是与癌症有关。已在 EGFR 的细胞内和细胞外区域鉴定出激活的肿瘤突变。讨论了这些肿瘤突变对理解 EGFR 激活及其抑制的影响。