5FTT

Octameric complex of Latrophilin 3 (Lec, Olf) , Unc5D (Ig, Ig2, TSP1) and FLRT2 (LRR)

5FTT の概要

• エントリーDOI: 10.2210/pdb5ftt/pdb
• 関連するPDBエントリー: 5FTU
• 分子名称: NETRIN RECEPTOR UNC5D, LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN FLRT2, ADHESION G PROTEIN-COUPLED RECEPTOR L3, ... (6 entities in total)
• 機能のキーワード: signaling protein, signalling protein, leucine-rich repeat, lrr, unc5, unc5d, flrt2, lphn3, lphn, adgrl, adgrl3, adgr, gpcr, uncoordinated-5, netrin receptor, flrt, latrophilin, adhesion, repulsion, guidance, beta propeller, immunoglobulin, thrombospondin, olfactomedin, lectin, octamer
• 由来する生物種: RATTUS NORVEGICUS (NORWAY RAT); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 318359.47

構造登録者

Jackson, V.A.,Mehmood, S.,Chavent, M.,Roversi, P.,Carrasquero, M.,del Toro, D.,Seyit-Bremer, G.,Ranaivoson, F.M.,Comoletti, D.,Sansom, M.S.P.,Robinson, C.V.,Klein, R.,Seiradake, E. (登録日: 2016-01-15, 公開日: 2016-05-04, 最終更新日: 2024-10-09)

主引用文献

Jackson, V.A.,Mehmood, S.,Chavent, M.,Roversi, P.,Carrasquero, M.,Del Toro, D.,Seyit-Bremer, G.,Ranaivoson, F.M.,Comoletti, D.,Sansom, M.S.P.,Robinson, C.V.,Klein, R.,Seiradake, E.
Super-Complexes of Adhesion Gpcrs and Neural Guidance Receptors
Nat.Commun., 7:11184-, 2016

PubMed Abstract: Latrophilin adhesion-GPCRs (Lphn1-3 or ADGRL1-3) and Unc5 cell guidance receptors (Unc5A-D) interact with FLRT proteins (FLRT1-3), thereby promoting cell adhesion and repulsion, respectively. How the three proteins interact and function simultaneously is poorly understood. We show that Unc5D interacts with FLRT2 in cis, controlling cell adhesion in response to externally presented Lphn3. The ectodomains of the three proteins bind cooperatively. Crystal structures of the ternary complex formed by the extracellular domains reveal that Lphn3 dimerizes when bound to FLRT2:Unc5, resulting in a stoichiometry of 1:1:2 (FLRT2:Unc5D:Lphn3). This 1:1:2 complex further dimerizes to form a larger 'super-complex' (2:2:4), using a previously undescribed binding motif in the Unc5D TSP1 domain. Molecular dynamics simulations, point-directed mutagenesis and mass spectrometry demonstrate the stability and molecular properties of these complexes. Our data exemplify how receptors increase their functional repertoire by forming different context-dependent higher-order complexes.

PubMed: 27091502
DOI: 10.1038/NCOMMS11184

実験手法

X-RAY DIFFRACTION (3.4 Å)