kinase / LRRK / multi-domain protein / GTPase / TRANSFERASE
機能・相同性
機能・相同性情報
negative regulation of peptidyl-tyrosine phosphorylation / positive regulation of intracellular signal transduction / osteoclast development / bone resorption / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of canonical Wnt signaling pathway / non-specific serine/threonine protein kinase / intracellular signal transduction / phosphorylation / protein serine kinase activity ...negative regulation of peptidyl-tyrosine phosphorylation / positive regulation of intracellular signal transduction / osteoclast development / bone resorption / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of canonical Wnt signaling pathway / non-specific serine/threonine protein kinase / intracellular signal transduction / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / GTP binding / mitochondrion / ATP binding / identical protein binding / membrane / metal ion binding / cytosol 類似検索 - 分子機能
National Institutes of Health/National Cancer Institute (NIH/NCI)
ZIA BC 011744
米国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structure and regulation of full-length human leucine-rich repeat kinase 1. 著者: Riley D Metcalfe / Juliana A Martinez Fiesco / Luis Bonet-Ponce / Jillian H Kluss / Mark R Cookson / Ping Zhang / 要旨: The human leucine-rich repeat kinases (LRRKs), LRRK1 and LRRK2 are large and unusually complex multi-domain kinases, which regulate fundamental cellular processes and have been implicated in human ...The human leucine-rich repeat kinases (LRRKs), LRRK1 and LRRK2 are large and unusually complex multi-domain kinases, which regulate fundamental cellular processes and have been implicated in human disease. Structures of LRRK2 have recently been determined, but the structure and molecular mechanisms regulating the activity of the LRRK1 as well as differences in the regulation of LRRK1 and LRRK2 remain unclear. Here, we report a cryo-EM structure of the LRRK1 monomer and a lower-resolution cryo-EM map of the LRRK1 dimer. The monomer structure, in which the kinase is in an inactive conformation, reveals key interdomain interfaces that control kinase activity as we validate experimentally. Both the LRRK1 monomer and dimer are structurally distinct compared to LRRK2. Overall, our results provide structural insights into the activation of the human LRRKs, which advance our understanding of their physiological and pathological roles.
選択した数: 3553719 詳細: Particles picked using a Topaz model trained on an initial LRRK1 dataset.
初期モデル
モデルのタイプ: NONE / 詳細: Ab-initio model generated using Cryosparc.
最終 再構成
解像度のタイプ: BY AUTHOR / 解像度: 3.92 Å / 解像度の算出法: FSC 0.143 CUT-OFF 詳細: Resolution given for map is the resolution of the global refinement map (D_1000269296). The resolution for the local refinement map was 3.94 (D_1000269298). 使用した粒子像数: 183273