Crystal Structure of the cGMP Dependent Protein Kinase II Leucine Zipper and Rab11b Complex Reveals Molecular Details of G-Kinase Specific Interactions. [Signal Transduction]
July 28th, 2014 by Reger, A. S., Yang, M. P., Koide-Yoshida, S., Guo, E., Mehta, S., Yuasa, K., Liu, A., Casteel, D. E., Kim, C.
cGMP-dependent protein kinase (PKG) interacting proteins (GKIPs) mediate cellular targeting of PKG isoforms by interacting with their leucine zipper (LZ) domains. These interactions prevent aberrant signaling cross talk between different PKG isotypes. To gain detailed insight into isotype-specific GKIP recognition by PKG, we analyzed the type II PKG LZ domain and found that residues 40 to 83 dimerized and specifically interacted with Rab11b. Next, we determined a crystal structure of the PKG II LZ-Rab11b complex. The PKG II LZ domain presents a mostly nonpolar surface onto which Rab11b docks, through Van der Waals interactions. Contact surfaces in Rab11b are found in the switch I, II, interswitch, and the β1/N-terminal regions. This binding surface dramatically differs from that seen in Rab11-FIP complex structures. Structural comparison with PKG Iα and Iβ LZs combined with mutagenic analysis reveals that GKIP recognition is mediated through surface charge interactions.