4X6R
An Isoform-specific Myristylation Switch Targets RIIb PKA Holoenzymes to Membranes
Summary for 4X6R
| Entry DOI | 10.2210/pdb4x6r/pdb |
| Related | 4X6Q |
| Descriptor | cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase type I-alpha regulatory subunit, SULFATE ION, ... (9 entities in total) |
| Functional Keywords | pka, membrane binding, molecular switch, transferase |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 2 |
| Total formula weight | 75071.27 |
| Authors | Zhang, P.,Ye, F.,Bastidas, A.C.,Kornev, A.P.,Ginsberg, M.H.,Wu, J.,Taylor, S.S. (deposition date: 2014-12-09, release date: 2015-07-22, Last modification date: 2020-06-24) |
| Primary citation | Zhang, P.,Ye, F.,Bastidas, A.C.,Kornev, A.P.,Wu, J.,Ginsberg, M.H.,Taylor, S.S. An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes. Structure, 23:1563-1572, 2015 Cited by PubMed Abstract: Cyclic AMP-dependent protein kinase (PKA) is regulated in part by N-terminal myristylation of its catalytic (C) subunit. Structural information about the role of myristylation in membrane targeting of PKA has been limited. In mammalian cells there are four functionally non-redundant PKA regulatory subunits (RIα, RIβ, RIIα, and RIIβ). PKA is assembled as an inactive R2C2 holoenzyme in cells. To explore the role of N-myristylation in membrane targeting of PKA holoenzymes, we solved crystal structures of RIα:myrC and RIIβ2:myrC2, and showed that the N-terminal myristylation site in the myrC serves as a flexible "switch" that can potentially be mobilized for membrane anchoring of RII, but not RI, holoenzymes. Furthermore, we synthesized nanodiscs and showed by electron microscopy that membrane targeting through the myristic acid is specific for the RII holoenzyme. This membrane-anchoring myristylation switch is independent of A Kinase Anchoring Proteins (AKAPs) that target PKA to membranes by other mechanisms. PubMed: 26278174DOI: 10.1016/j.str.2015.07.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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