The regulatory tandem domains of human phosphodiesterases 1 and 4 regulate a cyanobacterial adenylyl cyclase
| Autor: | Joachim E. Schultz, Ursula Kurz, Ana Banjac |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Calmodulin
ADCY9 Cell Biology Biology Cyanobacteria Cyclase ADCY10 Cyclic Nucleotide Phosphodiesterases Type 4 Protein Structure Tertiary Adenylyl cyclase Cyclic nucleotide chemistry.chemical_compound chemistry Biochemistry Phosphodiesterase I Biocatalysis biology.protein Humans Phosphorylation Protein kinase A Cyclase activity Adenylyl Cyclases |
| Zdroj: | Cellular Signalling. 24:1479-1484 |
| ISSN: | 0898-6568 |
| Popis: | Human phosphodiesterase 1 is regulated by a tandem of N-terminal calmodulin/Ca(2+)-binding domains. We grafted the tandems from hPDE1A3 and -B1 onto the cyanobacterial adenylyl cyclase CyaB1 thus replacing an intrinsic tandem GAF-domain. Cyclase activity was stimulated by Ca(2+)/calmodulin 1.9 to 4.4-fold, i.e. similarly as reported for hPDE1 regulation. hPDE4 long isoforms are activated by phosphorylation of a serine located in a conserved RRESF motif in a tandem of N-terminal upstream-conserved regions (UCR). We grafted the UCR tandems from hPDE4A4, -B1, and -D3 onto the CyaB1 cyclase as a reporter enzyme. Activity was enhanced 1.4 to 4.5-fold by respective phosphomimetic (S/D) point mutations. Similarly, cyclase activity was increased 2.5-fold by phosphorylation of the chimera with the PDE4D3 UCR tandem by cAMP-dependent protein kinase. We propose a common mechanism of activation in mammalian phosphodiesterases containing N-terminal tandem regulatory domains. A downstream region is suggested to alternate between random and ordered conformations and to enable switching between inactive, the catalytic domain occluding PDE homodimers and active monomeric PDE catalytic domains. |
| Databáze: | OpenAIRE |
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