8ARF

Crystal structure of the N-terminal parallel dimeric coiled-coil region of the human kinetochore associated protein Spindly

8ARF の概要

• エントリーDOI: 10.2210/pdb8arf/pdb
• 分子名称: Protein Spindly (1 entity in total)
• 機能のキーワード: kinetochore, dynein, dynactin, cell cycle
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24287.64

構造登録者

Perrakis, A.,Ahmad, M.U. (登録日: 2022-08-16, 公開日: 2022-09-07, 最終更新日: 2024-11-20)

主引用文献

d'Amico, E.A.,Ud Din Ahmad, M.,Cmentowski, V.,Girbig, M.,Muller, F.,Wohlgemuth, S.,Brockmeyer, A.,Maffini, S.,Janning, P.,Vetter, I.R.,Carter, A.P.,Perrakis, A.,Musacchio, A.
Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin.
J.Cell Biol., 221:-, 2022

PubMed Abstract: Cytoplasmic Dynein 1, or Dynein, is a microtubule minus end-directed motor. Dynein motility requires Dynactin and a family of activating adaptors that stabilize the Dynein-Dynactin complex and promote regulated interactions with cargo in space and time. How activating adaptors limit Dynein activation to specialized subcellular locales is unclear. Here, we reveal that Spindly, a mitotic Dynein adaptor at the kinetochore corona, exists natively in a closed conformation that occludes binding of Dynein-Dynactin to its CC1 box and Spindly motif. A structure-based analysis identified various mutations promoting an open conformation of Spindly that binds Dynein-Dynactin. A region of Spindly downstream from the Spindly motif and not required for cargo binding faces the CC1 box and stabilizes the intramolecular closed conformation. This region is also required for robust kinetochore localization of Spindly, suggesting that kinetochores promote Spindly activation to recruit Dynein. Thus, our work illustrates how specific Dynein activation at a defined cellular locale may require multiple factors.

PubMed: 36107127
DOI: 10.1083/jcb.202206131

実験手法

X-RAY DIFFRACTION (2.8 Å)