Notch Transmembrane Domain: Secondary Structure and Topology
Notch Transmembrane Domain: Secondary Structure and Topology
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DOI：
10.1021/acs.biochem.5b00456
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发表时间：
2015-06-16
期刊：
影响因子：
2.9
通讯作者：
Sanders, Charles R.
中科院分区：
文献类型：
--
作者：
Deatherage, Catherine L.;Lu, Zhenwei;Sanders, Charles R.
Notch信号通路在发育、神经元维持和造血中起关键作用。激活这一途径的必要步骤是γ分泌酶对其跨膜（TM）结构域的裂解。虽然可溶性结构域已经被广泛研究，但对其TM和侧翼近膜（JM）段的表征却很少。在这里，我们介绍了人类Notch1 TM/JM结构域的核磁共振（NMR）研究结果。TM结构域主要是α -螺旋结构。虽然侧翼的JM片段不采用规则的二级结构，但它们与膜表面相互作用，表明膜相互作用可能通过γ分泌酶和随后的NOTCH信号功能调节其切割。
The Notch signaling pathway is critical in development, neuronal maintenance, and hematopoiesis. An obligate step in the activation of this pathway is cleavage of its transmembrane (TM) domain by gamma-secretase. While the soluble domains have been extensively studied, little has been done to characterize its TM and flanking juxtamembrane (JM) segments. Here, we present the results of nuclear magnetic resonance (NMR) studies of the human Notch1 TM/JM domain. The TM domain is largely alpha-helical. While the flanking JM segments do not adopt regular secondary structure, they interact with the membrane surface, suggesting membrane interactions may play a role in modulating its cleavage by gamma-secretase and subsequent NOTCH signaling function.