Gα 螺旋域对信号的激活和失活：G 蛋白信号转导中长期被忽视的伙伴。
Signal activation and inactivation by the Gα helical domain: a long-neglected partner in G protein signaling.
机构信息
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
出版信息
Sci Signal. 2012 May 29;5(226):re2. doi: 10.1126/scisignal.2003013.
Abstract
Heterotrimeric guanine nucleotide-binding proteins (G proteins) are positioned at the top of many signal transduction pathways. The G protein α subunit is composed of two domains, one that resembles Ras and another that is composed entirely of α helices. Historically most attention has focused on the Ras-like domain, but emerging evidence reveals that the helical domain is an active participant in G protein signaling.
摘要
异三聚体鸟苷酸结合蛋白（G 蛋白）位于许多信号转导途径的顶端。G 蛋白α亚基由两个结构域组成，一个类似于 Ras，另一个完全由α螺旋组成。历史上，大多数注意力都集中在 Ras 样结构域上，但新出现的证据表明，螺旋结构域是 G 蛋白信号转导的积极参与者。
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2
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