The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors
The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors
复制标题
DOI：
10.1016/s1097-2765(03)00048-0
复制
发表时间：
2003-02-01
期刊：
影响因子：
16
通讯作者：
Ward, CW
中科院分区：
文献类型：
--
作者：
Garrett, TPJ;McKern, NM;Ward, CW
ErbB 2不结合配体，但似乎是其他ErbB受体的主要信号伴侣，通过与ErbB 1、ErbB 3或ErbB 4形成异聚复合物。ErbB 2残基1-509在2.5埃分辨率下的晶体结构揭示了与EGFR在与配体复合时类似的活化构象，并且与ErbB 3或EGFR的未活化形式中所见的非常不同。该结构解释了ErbB 2不能结合已知配体的原因，并提示了ErbB 2不能形成同源二聚体的原因。总之，这些数据表明了一个模型，其中ErbB 2已经处于活化构象，并准备与其他配体活化的ErbB受体相互作用。
ErbB2 does not bind ligand, yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB1, ErbB3, or ErbB4. The crystal structure of residues 1-509 of ErbB2 at 2.5 Angstrom resolution reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms of ErbB3 or EGFR. The structure explains the inability of ErbB2 to bind known ligands and suggests why ErbB2 fails to form homodimers. Together, the data suggest a model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors.