Adenyl cyclase system subunits

This toxin subunit is an enzyme, an ADP-ribo-syltransferase which catalyzes transfer of ADP-ribosyl units from the coenzyme NAD+ to specific arginine side chains to form N-ADP-ribosyl derivatives of various proteins. Of the proteins modified by cholera toxin, the most significant is the guanyl nucleotide regulatory protein Gs of the adenylate cyclase system.C/f/h ADP ribosylation of arginine 201 of the a subunit of protein Gs inhibits the GTP hydrolysis that normally allows the protein to relax to an unactivated form.e The ADP-ribosylated Gs keeps adenylate cyclase activated continuously and... 

Ax subunit which translocates within the cell membrane and activates the adenylate cyclase system. 

Adenyl cyclase systems isolated from mammals contain as a third component an additional guanosine triphosphate specific subunit and in all probability even more components whose function and structure are not known as yet. It is interesting to note that adenyl cyclases, Na-K-actlvated adenosine phosphatases (ATPases) have been located in the membrane of olfactory neurons and cAMP was found to have the highest concentration in man in the olfactory mucosa. 

The adenylate cyclase of brain particulate fraction, solubilized with Triton X-100, required CDR, Ca, and GTP in order to be activated by choleragen (Moss and Vaughan, 1977b). Use of Gpp(NH)p, CDR, and Ca " increased the adenylate cyclase activity, but choleragen had no effect. It appears that multiple protein factors may be involved in the activation of adenylate cyclase and that there may be multiple subunits of the adenylate cyclase system. 

Two AR subtypes, Ax and A3, couple through G to inhibit adenylate cyclase, while the other two subtypes, A2a and A2B, stimulate adenylate cyclase through Gs or G0if (for A2a). The A2BAR is also coupled to the activation of PLC through Gq. Furthermore, each of these receptors may couple through the (3,y subunits of the G proteins to other effector systems, including ion channels and phospholipases. Levels of intracellular... 

G0 was isolated as an other PTx-ribosylated G-protein which co-purifies with G, but which does not inhibit adenylate cyclase. There are two main isoforms (G0l and Go2), with additional splice-variants. G0 is particularly abundant in the nervous system, comprising up to 1% of membrane proteins. Its main function is to reduce the opening probability of those voltage-gated Ca2+ channels (N- and P/Q-type) involved in neurotransmitter release. Hence, it is largely responsible for the widespread auto-inhibition of transmitter secretion by presynaptic receptors and this effect is mediated through released py subunits. 

Three distinct G-proteins have been fully characterized. These are transducin (T), which allows rhodopsin to stimulate a high-affinity cyclic GMP phosphodiesterase upon photoactivation in retinal rods Gs, which allows receptors to stimulate the activity of adenylate cyclase and Gh which allows receptors to inhibit adenylate cyclase activity. These three G-proteins contain three non-identical subunits (a, /3 and y). It is their a subunits which provide the binding site for GTP as well as distinct sites for interaction with specific receptor and effector systems and for Mg2+. The /3 subunits associated with all three regulatory proteins are apparently identical although T has a different y subunit. 

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