Abstract:
:A kinase-anchoring proteins (AKAPs) target PKA to specific microdomains by using an amphipathic helix that docks to N-terminal dimerization and docking (D/D) domains of PKA regulatory (R) subunits. To understand specificity, we solved the crystal structure of the helical motif from D-AKAP2, a dual-specific AKAP, bound to the RIIalpha D/D domain. The 1.6 Angstrom structure reveals how this dynamic, hydrophobic docking site is assembled. A stable, hydrophobic docking groove is formed by the helical interface of two RIIalpha protomers. The flexible N terminus of one protomer is then recruited to the site, anchored to the peptide through two essential isoleucines. The other N terminus is disordered. This asymmetry provides greater possibilities for AKAP docking. Although there is strong discrimination against RIalpha in the N terminus of the AKAP helix, the hydrophobic groove discriminates against RIIalpha. RIalpha, with a cavity in the groove, can accept a bulky tryptophan, whereas RIIalpha requires valine.
journal_name
Mol Celljournal_title
Molecular cellauthors
Kinderman FS,Kim C,von Daake S,Ma Y,Pham BQ,Spraggon G,Xuong NH,Jennings PA,Taylor SSdoi
10.1016/j.molcel.2006.09.015subject
Has Abstractpub_date
2006-11-03 00:00:00pages
397-408issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(06)00663-0journal_volume
24pub_type
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