Structure of the membrane reconstituted transmembrane-juxtamembrane peptide EGFR(622-660) and its interaction with Ca2+/calmodulin
Structure of the membrane reconstituted transmembrane-juxtamembrane peptide EGFR(622-660) and its interaction with Ca2+/calmodulin
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DOI：
10.1021/bi061264m
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发表时间：
2006-10-24
期刊：
影响因子：
2.9
通讯作者：
Smith, Steven O.
中科院分区：
文献类型：
--
作者：
Sato, Takeshi;Pallavi, Payal;Smith, Steven O.
表皮生长因子受体（EGFR）的跨膜（TM）和跨膜（JM）区将细胞外结构域中的配体结合偶联至激酶结构域的活化。固态NMR和偏振FTIR测量的肽对应的TM加JM区域的EGFR（残基622-660）重建模型磷脂膜，以解决短的细胞质JM序列（残基645-660）在调节EGFR活性的作用。我们发现，TM域是螺旋过渡到非螺旋结构的TM-JM边界。荧光测量表明，EGFR的JM区域（622-660）与膜表面结合，并且该结合可以通过添加Ca 2+和钙调蛋白的复合物来逆转。这些数据共同支持EGFR的胞质JM区在调节受体活性中起积极作用的模型。
The transmembrane (TM) and juxtamembrane (JM) regions of the epidermal growth factor receptor ( EGFR) couple ligand binding in the extracellular domain to activation of the kinase domain. Solid-state NMR and polarized FTIR measurements of peptides corresponding to the TM plus JM regions of EGFR ( residues 622-660) reconstituted in model phospholipid membranes are presented to address the role of the short cytoplasmic JM sequence (residues 645-660) in regulating EGFR activity. We show that the TM domain is helical with a transition to non-helical structure at the TM-JM boundary. Fluorescence measurements indicate that the JM region of EGFR(622-660) binds to the membrane surface and that binding can be reversed by the addition of the complex of Ca2+ and calmodulin. Together these data support models suggesting the cytoplasmic JM region of EGFR plays an active role in regulating receptor activity.