6ra0

A ubiquitin-like dimerization domain controls protein kinase D activation by trans-autophosphorylation

spinqualitylabelsall models 6ra0, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ra0 is a 1 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Gene: dkf-1, W09C5.5 (CAEEL) Activity: Protein kinase C, with EC number 2.7.11.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DKF1_CAEEL] Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC (PubMed:16613841, PubMed:16613842). Role in the regulation of growth and neuromuscular control of movement (PubMed:16613841, PubMed:16613842). Involved in immune response to S.aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1 (PubMed:27184844). Publication Abstract from PubMed Protein kinase D (PKD) is an essential Ser/Thr kinase in animals and controls a variety of diverse cellular functions including vesicle trafficking and mitogenesis. PKD is activated by recruitment to membranes containing the lipid second messenger diacylglycerol (DAG) and subsequent phosphorylation of its activation loop. Here, we report the crystal structure of the PKD N-terminus at 2.2 A resolution containing a previously unannotated ubiquitin-like domain (ULD), which serves as a dimerization domain. A single point mutation in the dimerization interface of the ULD not only abrogated dimerization in cells, but also prevented PKD activation loop phosphorylation upon DAG production. We further show that the kinase domain of PKD dimerizes in a concentration-dependent manner and autophosphorylates on a single residue in its activation loop. We also provide evidence that PKD is expressed at concentrations two orders of magnitude below the ULD dissociation constant in mammalian cells. We therefore propose a new model for PKD activation in which the production of DAG leads to the local accumulation of PKD at the membrane, which drives ULD-mediated dimerization and subsequent trans-autophosphorylation of the kinase domain. A ubiquitin-like domain controls Protein Kinase D dimerization and activation by trans-autophosphorylation.,Elsner DJ, Siess KM, Gossenreiter T, Hartl M, Leonard TA J Biol Chem. 2019 Aug 12. pii: RA119.008713. doi: 10.1074/jbc.RA119.008713. PMID:31406020 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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