6RA0

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

6RA0 の概要

• エントリーDOI: 10.2210/pdb6ra0/pdb
• 分子名称: Serine/threonine-protein kinase dkf-1, ZINC ION (2 entities in total)
• 機能のキーワード: ubiquitin-like domain, zinc finger, dag-binding, c1, signaling protein
• 由来する生物種: Caenorhabditis elegans (roundworm)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17287.42

構造登録者

Elsner, D.J.,Leonard, T.A. (登録日: 2019-04-05, 公開日: 2019-08-14, 最終更新日: 2024-05-15)

主引用文献

Elsner, D.J.,Siess, K.M.,Gossenreiter, T.,Hartl, M.,Leonard, T.A.
A ubiquitin-like domain controls protein kinase D dimerization and activation by trans-autophosphorylation.
J.Biol.Chem., 294:14422-14441, 2019

PubMed Abstract: 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 Å 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 2 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.

PubMed: 31406020
DOI: 10.1074/jbc.RA119.008713

実験手法

X-RAY DIFFRACTION (2.26 Å)