Related protein-protein interaction modules present drastically different surface topographies despite a conserved helical platform.
The subcellular localization of cAMP-dependent protein kinase (PKA) occurs through interaction with A-Kinase Anchoring Proteins (AKAPs). AKAPs bind to the PKA regulatory subunit dimer of both type Ialpha and type IIalpha (RIalpha and RIIalpha). RIalpha and RIIalpha display characteristic localization within different cell types, which is maintained by interaction of AKAPs with the N-terminal dimerization and docking domain (D/D) of the respective regulatory subunit. Previously, we reported the solution structure of RIIa D/D module, both free and bound to AKAPs. We have now solved the solution structure of the dimerization and docking domain of the type Ialpha regulatory dimer subunit (RIalpha D/D). RIalpha D/D is a compact docking module, with unusual interchain disulfide bonds that help maintain the AKAP interaction surface. In contrast to the shallow hydrophobic groove for AKAP binding across the surface of the RIIalpha D/D dimeric interface, the RIalpha D/D module presents a deep cleft for proposed AKAP binding. RIalpha and RIIalpha D/D interaction modules present drastically differing dimeric topographies, despite a conserved X-type four-helix bundle structure.
Banky
Poopak
P
Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093-0359, USA.
Roy
Melinda
M
Newlon
Marceen G
MG
Morikis
Dimitrios
D
Haste
Nina M
NM
Taylor
Susan S
SS
Jennings
Patricia A
PA
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid
D004220:Disulfides; D020033:Protein Isoforms; D017868:Cyclic AMP-Dependent Protein Kinases; D003545:Cysteine