5YVI

Crystal structure of Karyopherin beta2 in complex with FUS(456-526)

5YVI の概要

• エントリーDOI: 10.2210/pdb5yvi/pdb
• 分子名称: Transportin-1, RNA-binding protein FUS (2 entities in total)
• 機能のキーワード: importin family, protein transport, protein transport-rna binding protein complex, protein transport/rna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: Q92973; Nucleus : P35637
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 105886.39

構造登録者

Yoshizawa, T.,Fung, H.Y.J.,Chook, Y.M. (登録日: 2017-11-25, 公開日: 2018-05-16, 最終更新日: 2023-11-22)

主引用文献

Yoshizawa, T.,Ali, R.,Jiou, J.,Fung, H.Y.J.,Burke, K.A.,Kim, S.J.,Lin, Y.,Peeples, W.B.,Saltzberg, D.,Soniat, M.,Baumhardt, J.M.,Oldenbourg, R.,Sali, A.,Fawzi, N.L.,Rosen, M.K.,Chook, Y.M.
Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites.
Cell, 173:693-705.e22, 2018

PubMed Abstract: Liquid-liquid phase separation (LLPS) is believed to underlie formation of biomolecular condensates, cellular compartments that concentrate macromolecules without surrounding membranes. Physical mechanisms that control condensate formation/dissolution are poorly understood. The RNA-binding protein fused in sarcoma (FUS) undergoes LLPS in vitro and associates with condensates in cells. We show that the importin karyopherin-β2/transportin-1 inhibits LLPS of FUS. This activity depends on tight binding of karyopherin-β2 to the C-terminal proline-tyrosine nuclear localization signal (PY-NLS) of FUS. Nuclear magnetic resonance (NMR) analyses reveal weak interactions of karyopherin-β2 with sequence elements and structural domains distributed throughout the entirety of FUS. Biochemical analyses demonstrate that most of these same regions also contribute to LLPS of FUS. The data lead to a model where high-affinity binding of karyopherin-β2 to the FUS PY-NLS tethers the proteins together, allowing multiple, distributed weak intermolecular contacts to disrupt FUS self-association, blocking LLPS. Karyopherin-β2 may act analogously to control condensates in diverse cellular contexts.

PubMed: 29677513
DOI: 10.1016/j.cell.2018.03.003

実験手法

X-RAY DIFFRACTION (2.9 Å)