scholarly journals A structural motif that defines the ATP-regulatory module of guanylate cyclase in atrial natriuretic factor signalling

1992 ◽  
Vol 282 (2) ◽  
pp. 533-537 ◽  
Author(s):  
R M Goraczniak ◽  
T Duda ◽  
R K Sharma
Keyword(s):  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Catalytic Domain ◽  
Structural Motif ◽  
Activation Process ◽  
Single Chain ◽  
Natriuretic Factor ◽  
Expression Studies ◽  
Regulatory Module ◽  
Atrial Natriuretic

Atrial natriuretic factor (ANF)-dependent guanylate cyclase is a single-chain transmembrane-spanning protein, containing an ANF receptor and having catalytic activity. ANF binding to the receptor domain activates the catalytic domain, generating the second messenger cyclic GMP. Obligatory in this activation process is an intervening step regulated by ATP, but its mechanism is not known. Through a programme of site-directed and deletion mutagenesis/expression studies, we report herein the identity of a structural motif (Gly503-Arg-Gly-Ser-Asn-Tyr-Gly509) that binds ATP and amplifies the ANF-dependent cyclase activity; this, therefore, represents an ATP-regulatory module (ARM) of the enzyme, which plays a pivotal role in ANF signalling.

Allosteric regulatory step and configuration of the ATP-binding pocket in atrial natriuretic factor receptor guanylate cyclase transduction mechanism

2001 ◽  
Vol 79 (8) ◽  
pp. 682-691 ◽  
Author(s):  
Rameshwar K Sharma ◽  
Prem Yadav ◽  
Teresa Duda
Keyword(s):  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Catalytic Domain ◽  
Binding Pocket ◽  
Atp Binding ◽  
Transduction Mechanism ◽  
Natriuretic Factor ◽  
Regulatory Module ◽  
Atrial Natriuretic Factor Receptor ◽  
Atrial Natriuretic

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.Key words: ANF, ANF-receptor guanylate cyclase (ANF-RGC), ATP, ATP-regulatory module (ARM).

Response of guanylate cyclase to atrial natriuretic factor in epithelial cells of the frog choroid plexus

1995 ◽  
Vol 27 (2) ◽  
pp. 233-240 ◽  
Author(s):  
S. Tei ◽  
D. Vagnetti ◽  
T. Secca ◽  
B. Santarella ◽  
C. Roscani ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

scholarly journals Stimulation of guanylate cyclase by atrial natriuretic factor in isolated human glomeruli

FEBS Letters ◽  
1985 ◽  
Vol 189 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Nicole Ardaillou ◽  
Marie-Paule Nivez ◽  
Raymond Ardaillou
Keyword(s):  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Stimulation Of ◽  
Atrial Natriuretic

Biochemical mechanisms of atrial natriuretic factor action

1989 ◽  
Vol 67 (9) ◽  
pp. 1124-1129 ◽  
Author(s):  
Johanne Tremblay ◽  
Pavel Hamet
Keyword(s):  
Heart Failure ◽  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Soluble Guanylate Cyclase ◽  
Membrane Glycoprotein ◽  
Natriuretic Factor ◽  
Biochemical Mechanisms ◽  
Stimulation Of ◽  
Atrial Natriuretic

Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase–cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase by such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase–cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF–cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated.Key words: ANF, cGMP, guanylate cyclase, hypertension, heart failure.

Lung atrial natriuretic factor (ANF) and guanylate cyclase (GC) in UM-X7.1 hamsters

1990 ◽  
Vol 22 ◽  
pp. S93
Author(s):  
Paolo Di Nardo ◽  
Marilena Minieri ◽  
Daniela Vagnetti ◽  
Daniela Carbonari ◽  
Giuseppe Peruzzi ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Atrial Natriuretic
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