Sharma R K, Yadav P, Duda T
Department of Cell Biology, NJMS & SOM, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA.
Can J Physiol Pharmacol. 2001 Aug;79(8):682-91.
The atrial natriuretic factor (ANF) signal transduction mechanism consists of the transformation of the signal information into the production of cyclic GMP. The binding of ANF to its receptor, which is also a guanylate cyclase, generates the signal. This cyclase has been termed atrial natriuretic factor receptor guanylate cyclase, ANF-RGC. ANF-RGC is a single transmembrane-spanning protein. The ANF receptor domain resides in the extracellular region of the protein, and the catalytic domain is located in the intracellular region at the C-terminus of the protein. Thus, the signal is relayed progressively from the receptor domain to the catalytic domain, where it is converted into the formation of cyclic GMP. The first transduction step is the direct binding of ATP with ANF-RGC. This causes allosteric regulation of the enzyme and primes it for the activation of its catalytic moiety. The partial structural motif of the ATP binding domain in ANF-RGC has been elucidated, and it has been named ATP regulatory module (ARM). In this presentation, we provide a brief review of the ATP-regulated transduction mechanism and the ARM model. The model depicts a configuration of the ATP-binding pocket that has been experimentally validated, and the model shows that the ATP-dependent transduction process is a two- (or more) step event. The first step involves the binding of ATP with its ARM. This partially activates the cyclase and prepares it for the subsequent steps, which are consistent with its being phosphorylated and attaining the fully activated state.
心房利钠因子（ANF）信号转导机制包括将信号信息转化为环鸟苷酸（cGMP）的产生。ANF与其受体（也是一种鸟苷酸环化酶）结合产生信号。这种环化酶被称为心房利钠因子受体鸟苷酸环化酶，即ANF-RGC。ANF-RGC是一种单次跨膜蛋白。ANF受体结构域位于该蛋白的细胞外区域，催化结构域位于该蛋白C末端的细胞内区域。因此，信号从受体结构域逐步传递到催化结构域，在那里它被转化为环鸟苷酸的形成。第一步转导是ATP与ANF-RGC的直接结合。这会引起该酶的变构调节，并使其催化部分准备好被激活。ANF-RGC中ATP结合结构域的部分结构基序已被阐明，并被命名为ATP调节模块（ARM）。在本报告中，我们简要回顾了ATP调节的转导机制和ARM模型。该模型描绘了一个已通过实验验证的ATP结合口袋的结构，并且该模型表明ATP依赖性转导过程是一个两步（或更多步）事件。第一步涉及ATP与其ARM的结合。这会部分激活环化酶，并为后续步骤做好准备，后续步骤与其被磷酸化并达到完全激活状态一致。
