4GRV

The crystal structure of the neurotensin receptor NTS1 in complex with neurotensin (8-13)

4GRV の概要

• エントリーDOI: 10.2210/pdb4grv/pdb
• 分子名称: Neurotensin receptor type 1, lysozyme chimera, Neurotensin 8-13, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: g-protein coupled receptor, neurotensin receptor, g-protein, signaling protein-agonist complex, signaling protein/agonist
• 由来する生物種: Rattus norvegicus (Rat, Bacteriaphage T4); 詳細
• 細胞内の位置: Cell membrane ; Multi- pass membrane protein : P20789
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58497.58

構造登録者

Noinaj, N.,White, J.F.,Shibata, Y.,Love, J.,Kloss, B.,Xu, F.,Gvozdenovic-Jeremic, J.,Shah, P.,Shiloach, J.,Tate, C.G.,Grisshammer, R. (登録日: 2012-08-27, 公開日: 2012-10-17, 最終更新日: 2024-11-20)

主引用文献

White, J.F.,Noinaj, N.,Shibata, Y.,Love, J.,Kloss, B.,Xu, F.,Gvozdenovic-Jeremic, J.,Shah, P.,Shiloach, J.,Tate, C.G.,Grisshammer, R.
Structure of the agonist-bound neurotensin receptor.
Nature, 490:508-513, 2012

PubMed Abstract: Neurotensin (NTS) is a 13-amino-acid peptide that functions as both a neurotransmitter and a hormone through the activation of the neurotensin receptor NTSR1, a G-protein-coupled receptor (GPCR). In the brain, NTS modulates the activity of dopaminergic systems, opioid-independent analgesia, and the inhibition of food intake; in the gut, NTS regulates a range of digestive processes. Here we present the structure at 2.8 Å resolution of Rattus norvegicus NTSR1 in an active-like state, bound to NTS(8-13), the carboxy-terminal portion of NTS responsible for agonist-induced activation of the receptor. The peptide agonist binds to NTSR1 in an extended conformation nearly perpendicular to the membrane plane, with the C terminus oriented towards the receptor core. Our findings provide, to our knowledge, the first insight into the binding mode of a peptide agonist to a GPCR and may support the development of non-peptide ligands that could be useful in the treatment of neurological disorders, cancer and obesity.

PubMed: 23051748
DOI: 10.1038/nature11558

実験手法

X-RAY DIFFRACTION (2.802 Å)