Bioinformatic analysis of fungal regulatory subunit of cAMP-dependent protein kinase

RINALDI, J., ROSSI, S. Y MORENO, S.

Buenos Aires

Congreso; 2das Jornadas Iberoamericanas de Informática; 2006

Red Iberoamericana de Bioinformatica

Higher eukaryotes regulatory subunits are modular: they consist of a dimerization domain (DD) at the NH2 terminus and two-tandem cAMP-binding domains (CBD) at the COOH terminus, joined by a flexible linker or hinge, which includes a substrate-like inhibitory site. The aim of this work is to find out if the same domains are present in fungal regulatory subunits and to compare among them. To approach this goal we collected fungal R subunit sequences and performed sequence alignment and prediction of conserved domains, low complexity sequences and phosphorylation and protein-protein interaction sites. CBDs were predicted in all sequences while just in some of them a DD was found.  All the organisms that lack a predicted DD belong to the same Pezizomycotina group of Ascomycota Division. From the separate alignment of each domain or region we verified that DD and both CBD were well conserved among fungi and also similar to bovine RI-alpha, RII-alpha and RII-beta and that there was a striking diversity in the linker region. To analyze the linker region we decided to separate the sequences into two groups: those that have a predicted DD (DD+) and those that lack it (DD-). The DD- group sequences are relatively more conserved than the one of the DD+ group. This conservation is especially important toward the COOH-terminus of the inhibitory site. A conserved Thr/Ser is predicted to be a likely phosphorylation site for proline dependent Ser/Thr kinase as Cdk5 y Cdc2. In addition, a conserved polyproline region is predicted to bind the Abl SH3 domains. Low complexity sequences are more abundant in the DD+ group than in the DD- group. This kind of separate alignment allows unveiling similarities and the divergences that are not seen in the alignment of the whole sequence.