5F2U

Structure of Fully modified farnesylated INPP5E Peptide in complex with PDE6D

5F2U の概要

• エントリーDOI: 10.2210/pdb5f2u/pdb
• 分子名称: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta, Phosphatidylinositol 4,5-bisphosphate 5-phosphatase, s-farnesyl-l-cysteine methyl ester, FARNESYL, ... (4 entities in total)
• 機能のキーワード: lipid binding protein, immunoglobulin-like, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, cytosol : O43924
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 36079.52

構造登録者

Fansa, E.K.,Isamil, S.,Wittinghofer, A. (登録日: 2015-12-02, 公開日: 2016-04-13, 最終更新日: 2024-01-10)

主引用文献

Fansa, E.K.,Koesling, S.K.,Zent, E.,Wittinghofer, A.,Ismail, S.
PDE6delta-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity.
Nat Commun, 7:11366-, 2016

PubMed Abstract: The phosphodiesterase 6 delta subunit (PDE6δ) shuttles several farnesylated cargos between membranes. The cargo sorting mechanism between cilia and other compartments is not understood. Here we show using the inositol polyphosphate 5'-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6δ and the specificity of cargo release. High-affinity cargo is exclusively released by the ciliary transport regulator Arl3, while low-affinity cargo is released by Arl3 and its non-ciliary homologue Arl2. Structures of PDE6δ/cargo complexes reveal the molecular basis of the sorting signal which depends on the residues at the -1 and -3 positions relative to farnesylated cysteine. Structure-guided mutation allows the generation of a low-affinity INPP5E mutant which loses exclusive ciliary localization. We postulate that the affinity to PDE6δ and the release by Arl2/3 in addition to a retention signal are the determinants for cargo sorting and enrichment at its destination.

PubMed: 27063844
DOI: 10.1038/NCOMMS11366

実験手法

X-RAY DIFFRACTION (1.85 Å)