9BFR

Cryo-EM structure of Bride of Sevenless extracellular domain (dimer, Sevenless-bound form)

9BFR の概要

• エントリーDOI: 10.2210/pdb9bfr/pdb
• 関連するPDBエントリー: 9BFP 9BFQ 9BFS 9BFU
• EMDBエントリー: 44504
• 分子名称: Protein bride of sevenless, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: bride of sevenless, boss, gpcr, g-protein coupled receptor, drosophila, eye development, vision, photoreceptor, glucose metabolism, signaling protein
• 由来する生物種: Drosophila melanogaster (fruit fly)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 115884.69

構造登録者

Cerutti, G.,Shapiro, L. (登録日: 2024-04-18, 公開日: 2025-01-29, 最終更新日: 2025-05-14)

主引用文献

Cerutti, G.,Arias, R.,Bahna, F.,Mannepalli, S.,Katsamba, P.S.,Ahlsen, G.,Kloss, B.,Bruni, R.,Tomlinson, A.,Shapiro, L.
Structures and pH-dependent dimerization of the sevenless receptor tyrosine kinase.
Mol.Cell, 84:4677-4690.e6, 2024

PubMed Abstract: Sevenless (Sev) is a Drosophila receptor tyrosine kinase (RTK) required for the specification of the R7 photoreceptor. It is cleaved into α and β subunits and binds the ectodomain of the G-protein-coupled receptor bride of sevenless (Boss). Previous work showed that the Boss ectodomain could bind but not activate Sev; rather, the whole seven-pass transmembrane Boss was required. Here, we show that Sev does not need to be cleaved to function and that a single-pass transmembrane form of Boss activates Sev. We use cryo-electron microscopy and biophysical methods to determine the structural basis of ligand binding and pH-dependent dimerization of Sev, and we discuss the implications in the process of Sev activation. The Sev human homolog, receptor oncogene from sarcoma 1 (ROS1), is associated with oncogenic transformations, and we discuss their structural similarities.

PubMed: 39510067
DOI: 10.1016/j.molcel.2024.10.017

実験手法

ELECTRON MICROSCOPY (3.19 Å)