8CX6

TPX2 Minimal Active Domain on Microtubules

8CX6 の概要

• エントリーDOI: 10.2210/pdb8cx6/pdb
• NMR情報: BMRB: 31025
• 分子名称: Targeting protein for Xklp2-A (1 entity in total)
• 機能のキーワード: spindle assembly factor, branching microtubule nucleation, cell cycle
• 由来する生物種: Xenopus laevis (African clawed frog)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28443.77

構造登録者

Guo, C.,Alfaro-Aco, R.,Russell, R.,Zhang, C.,Petry, S.,Polenova, T. (登録日: 2022-05-19, 公開日: 2023-06-28, 最終更新日: 2024-05-15)

主引用文献

Guo, C.,Alfaro-Aco, R.,Zhang, C.,Russell, R.W.,Petry, S.,Polenova, T.
Structural basis of protein condensation on microtubules underlying branching microtubule nucleation.
Nat Commun, 14:3682-3682, 2023

PubMed Abstract: Targeting protein for Xklp2 (TPX2) is a key factor that stimulates branching microtubule nucleation during cell division. Upon binding to microtubules (MTs), TPX2 forms condensates via liquid-liquid phase separation, which facilitates recruitment of microtubule nucleation factors and tubulin. We report the structure of the TPX2 C-terminal minimal active domain (TPX2) on the microtubule lattice determined by magic-angle-spinning NMR. We demonstrate that TPX2 forms a co-condensate with soluble tubulin on microtubules and binds to MTs between two adjacent protofilaments and at the intersection of four tubulin heterodimers. These interactions stabilize the microtubules and promote the recruitment of tubulin. Our results reveal that TPX2 is disordered in solution and adopts a folded structure on MTs, indicating that TPX2 undergoes structural changes from unfolded to folded states upon binding to microtubules. The aromatic residues form dense interactions in the core, which stabilize folding of TPX2 on microtubules. This work informs on how the phase-separated TPX2 behaves on microtubules and represents an atomic-level structural characterization of a protein that is involved in a condensate on cytoskeletal filaments.

PubMed: 37344496
DOI: 10.1038/s41467-023-39176-z

実験手法

SOLID-STATE NMR