2QV2

A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway

2QV2 の概要

• エントリーDOI: 10.2210/pdb2qv2/pdb
• 分子名称: Inositol polyphosphate 5-phosphatase OCRL-1 (2 entities in total)
• 機能のキーワード: endocytosis, clathrin, appl1, phosphoinositide, ash, rhogap, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasmic vesicle, phagosome membrane (By similarity): Q01968
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39470.23

構造登録者

Mao, Y.,Erdman, K.S.,McCrea, H.J.,De Camilli, P. (登録日: 2007-08-07, 公開日: 2007-08-21, 最終更新日: 2024-02-21)

主引用文献

Erdmann, K.S.,Mao, Y.,McCrea, H.J.,Zoncu, R.,Lee, S.,Paradise, S.,Modregger, J.,Biemesderfer, D.,Toomre, D.,De Camilli, P.
A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway
Dev.Cell, 13:377-390, 2007

PubMed Abstract: Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, whose manifestations include mental retardation and renal Fanconi syndrome. OCRL has been implicated in membrane trafficking, but disease mechanisms remain unclear. We show that OCRL visits late-stage, endocytic clathrin-coated pits and binds the Rab5 effector APPL1 on peripheral early endosomes. The interaction with APPL1, which is mediated by the ASH-RhoGAP-like domains of OCRL and is abolished by disease mutations, provides a link to protein networks implicated in the reabsorptive function of the kidney and in the trafficking and signaling of growth factor receptors in the brain. Crystallographic studies reveal a role of the ASH-RhoGAP-like domains in positioning the phosphatase domain at the membrane interface and a clathrin box protruding from the RhoGAP-like domain. Our results support a role of OCRL in the early endocytic pathway, consistent with the predominant localization of its preferred substrates, PI(4,5)P(2) and PI(3,4,5)P(3), at the cell surface.

PubMed: 17765681
DOI: 10.1016/j.devcel.2007.08.004

実験手法

X-RAY DIFFRACTION (2.4 Å)