一种自激活 G 蛋白 α 亚基的晶体结构揭示了其信号起始的独特机制。
The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation.
机构信息
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
出版信息
Sci Signal. 2011 Feb 8;4(159):ra8. doi: 10.1126/scisignal.2001446.
In animals, heterotrimeric guanine nucleotide-binding protein (G protein) signaling is initiated by G protein-coupled receptors (GPCRs), which activate G protein α subunits; however, the plant Arabidopsis thaliana lacks canonical GPCRs, and its G protein α subunit (AtGPA1) is self-activating. To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals.
在动物中，三聚体鸟苷酸结合蛋白（G 蛋白）信号转导由 G 蛋白偶联受体（GPCR）启动，GPCR 激活 G 蛋白 α 亚基；然而，植物拟南芥缺乏典型的 GPCR，其 G 蛋白 α 亚基（AtGPA1）是自我激活的。为了研究 AtGPA1 如何被激活，我们测定了其晶体结构。AtGPA1 的结构与动物 G 蛋白 α 亚基相似，但我们的晶体学和生物物理研究表明，它具有不同的特性。值得注意的是，AtGPA1 的螺旋结构域表现出明显的固有无序性，并倾向于与蛋白的 Ras 结构域脱离。结构域取代实验表明，AtGPA1 的螺旋结构域对于自我激活是必需的，并且足以赋予动物 G 蛋白 α 亚基自我激活能力。这些发现揭示了拟南芥中 G 蛋白激活的结构基础，与在动物中发现的成熟机制不同。
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