title: Induction of flexibility through protein-protein interactions.
abstract: The dimerization/docking (D/D) domain of the cyclic AMP-dependent protein kinase (PKA) holoenzyme mediates important protein-protein interactions that direct the subcellular localization of the enzyme. A kinase anchoring proteins (AKAPs) provide the molecular scaffold for the localization of PKA. The recent solution structures of two D/D AKAP complexes revealed that the AKAP binds to a surface-exposed, hydrophobic groove on the D/D. In the present study, we present an analysis of the changes in hydrogen/deuterium exchange protection and internal motions of the backbone of the D/D when free and bound to the prototype anchoring protein, Ht31(pep). We observe that formation of the complex results in significant, but small, increases in H/D exchange protection factors as well as increases in backbone flexibility, throughout the D/D, and in particular, in the hydrophobic binding groove. This unusual observation of increased backbone flexibility and marginal H/D exchange protection, despite high affinity protein-ligand interactions, may be a general effect observed for the stabilization of hydrophobic ligand/hydrophobic pocket interactions.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fayos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Melacini
authors.forename: Marceen G
authors.initials: MG
authors.lastname: Newlon
authors.forename: Lora
authors.initials: L
authors.lastname: Burns
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jennings
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001669:Biochemical Phenomena; D001671:Biochemistry; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D010455:Peptides; C470173:ROPN1L protein, human; D006859:Hydrogen