7UR2

Crystal structure of the Sec14 domain of the RhoGEF Kalirin

7UR2 の概要

• エントリーDOI: 10.2210/pdb7ur2/pdb
• 分子名称: Isoform 7 of Kalirin, SULFATE ION (3 entities in total)
• 機能のキーワード: ras homologous guanine nucleotide exchange factor, cral-trio domain, spectrin repeat, lysophospholipids, lipid binding protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 174612.95

構造登録者

Li, Y.,Doukov, T.I.,Hao, B. (登録日: 2022-04-21, 公開日: 2023-01-18, 最終更新日: 2024-05-22)

主引用文献

Li, Y.,Pustovalova, Y.,Doukov, T.I.,Hoch, J.C.,Mains, R.E.,Eipper, B.A.,Hao, B.
Structure of the Sec14 domain of Kalirin reveals a distinct class of lipid-binding module in RhoGEFs.
Nat Commun, 14:96-96, 2023

PubMed Abstract: Gated entry of lipophilic ligands into the enclosed hydrophobic pocket in stand-alone Sec14 domain proteins often links lipid metabolism to membrane trafficking. Similar domains occur in multidomain mammalian proteins that activate small GTPases and regulate actin dynamics. The neuronal RhoGEF Kalirin, a central regulator of cytoskeletal dynamics, contains a Sec14 domain (Kal) followed by multiple spectrin-like repeats and catalytic domains. Previous studies demonstrated that Kalirin lacking its Sec14 domain fails to maintain cell morphology or dendritic spine length, yet whether and how Kal interacts with lipids remain unknown. Here, we report the structural and biochemical characterization of Kal. Kal adopts a closed conformation, sealing off the canonical ligand entry site, and instead employs a surface groove to bind a limited set of lysophospholipids. The low-affinity interactions of Kal with lysolipids are expected to serve as a general model for the regulation of Rho signaling by other Sec14-containing Rho activators.

PubMed: 36609407
DOI: 10.1038/s41467-022-35678-4

実験手法

X-RAY DIFFRACTION (1.89 Å)