Duda T, Sharma R K
Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141, USA.
Biochem Biophys Res Commun. 1995 Apr 6;209(1):286-92. doi: 10.1006/bbrc.1995.1501.
Atrial natriuretic factor (ANF)-dependent guanylate cyclase (ANF-RGC) is a single-chain transmembrane-spanning protein, containing both ANF binding and catalytic cyclase activity. ANF binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Obligatory in this activation process is an intervening step regulated by the ATP binding to the cyclase. This is a signal transduction step that bridges the events of ligand binding and cyclase activation. A defined structural motif (Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509), termed ATP regulatory module (ARM), is critical for this step. The present study shows that the ARM-Gly505 residue acts as an ATP bimodal switch in regulating both the ligand binding and signal transduction activities of ANF-RGC, thus representing a critical site to turn the hormone signal on and off.
心房利钠因子（ANF）依赖性鸟苷酸环化酶（ANF-RGC）是一种单链跨膜蛋白，兼具ANF结合活性和催化性环化酶活性。ANF与细胞外受体结构域结合会激活胞质催化结构域，生成第二信使环磷酸鸟苷（cGMP）。在这一激活过程中，一个由ATP与环化酶结合调控的中间步骤必不可少。这是一个连接配体结合事件和环化酶激活事件的信号转导步骤。一个特定的结构基序（Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509），称为ATP调节模块（ARM），对这一步骤至关重要。本研究表明，ARM-Gly505残基在调节ANF-RGC的配体结合和信号转导活性方面起着ATP双模态开关的作用，因此是开启和关闭激素信号的关键位点。
