title: Crystal structure of the cGMP-dependent protein kinase II leucine zipper and Rab11b protein complex reveals molecular details of G-kinase-specific interactions.
abstract: 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 leucine zipper domain and found that residues 40-83 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 switch I and II, interswitch, and the β1/N-terminal regions. This binding surface dramatically differs from that seen in the Rab11 family of interacting protein complex structures. Structural comparison with PKG Iα and Iβ LZs combined with mutagenic analysis reveals that GKIP recognition is mediated through surface charge interactions.
authors: From the Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
authors: Albert S
authors: AS
authors: Reger
authors: the Departments of Biochemistry and.
authors: Matthew P
authors: MP
authors: Yang
authors: the Department of Biological Science and Technology, University of Tokushima Graduate School, Tokushima 770-8506, Japan.
authors: Shizuyo
authors: S
authors: Koide-Yoshida
authors: Chemistry, Rice University, Houston, Texas 77005.
authors: Elaine
authors: E
authors: Guo
authors: From the Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
authors: Shrenik
authors: S
authors: Mehta
authors: the Department of Biological Science and Technology, University of Tokushima Graduate School, Tokushima 770-8506, Japan.
authors: Keizo
authors: K
authors: Yuasa
authors: the Department of Medicine, University of California at San Diego, La Jolla, California 92093, and.
authors: Alan
authors: A
authors: Liu
authors: the Department of Medicine, University of California at San Diego, La Jolla, California 92093, and.
authors: Darren E
authors: DE
authors: Casteel
authors: From the Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, the Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 ckim@bcm.edu.
authors: Choel
authors: C
authors: Kim
mesh_terms: D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000737:chemistry; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D000099193:rab11 GTP-Binding Proteins
chemical_list: D006152:Cyclic GMP; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D046912:Multiprotein Complexes; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
keywords: Cyclic GMP (cGMP); G-kinase-interacting Protein (GKIP); Protein Kinase G (PKG); Protein-Protein Interaction; Rab; Second Messenger; Serine/Threonine Protein Kinase; Signal Transduction; Type II cGMP-dependent Protein Kinase (PKG II)