Schu275/45

"Charakterisierung einer neuen Klasse von Rezeptoren: Identifizierung der Liganden der Membranre-zeptoren der Klasse IIIa Adenylatcyclasen des Menschen."

01.03.2021 bis 30.06.2024

Adenylate cyclases (ACs) are evolutionarily old proteins that produce the almost universal second messenger 3’,5’-cyclic-adenosine-monophosphate (cAMP). The most predominant class III ACs are already present in cyanobacteria and are widespread in many bacterial phyla. Eukaryotes contain class III ACs which were derived from and are closely related to the bacterial ones. Most members of the class III AC family are membrane delimited proteins forming a catalytic dimer. In mammals 9 out of 10 class III ACs are pseudoheterodimers and possess two particular hexahelical membrane domains (TM1 and TM2), resulting in a membrane anchor with a total of 12 helical spans. The potential functions of the membrane-anchoring domains of mammalian ACs are unknown. We worked with two mycobacterial class III ACs (Rv3645 and Rv1625c) which are monomeric and require dimerization to be active. Our data, published since 2021, showed that in principle the cytosolic class III AC catalytic domains can be regulated by its membrane-anchor/receptor. We wish to identify the ligands for the AC membrane receptors which have been characterized a lipophilic chemicals.