Fig. 1 Architecture of PKA-C and locations of the Cushing’s syndrome mutations. Architecture of PKA-C and locations of the Cushing’s syndrome mutations.

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Presentation transcript:

Fig. 1 Architecture of PKA-C and locations of the Cushing’s syndrome mutations. Architecture of PKA-C and locations of the Cushing’s syndrome mutations. (A) Structure of PKA-C [Protein Data Bank (PDB) ID: 1ATP] in complex with pseudo-substrate PKI depicting the location of Cushing’s mutations (yellow spheres) in relation to structural elements of the kinase. The E248Q mutation includes an additional deletion (del243-247), and the S212R mutation includes an insertion (insIILR) not depicted. (B) X-ray structure of PKA-CL205R (PDB ID: 4WB6) with the overlay of PKI5–24 (PKIWT from PDB ID: 1ATP) describing the architecture of the peptide binding site and steric clash between kinase (PKA-CL205R) and pseudo-substrate. (C) Structure of the R/C complex (PDB ID: 2QCS) depicting locations of Cushing’s mutations in relation to the pseudo-substrate inhibitory sequence of the R-subunit. (D) Primary sequence comparison of common regulators (RIα, RIIβ, and PKI) and peptide substrates of the catalytic subunit (Kemptide and VPS36). Caitlin Walker et al. Sci Adv 2019;5:eaaw9298 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).