5YVH

Crystal structure of Karyopherin beta2 in complex with FUS(371-526)

Summary for 5YVH

• Entry DOI: 10.2210/pdb5yvh/pdb
• Descriptor: Transportin-1, RNA-binding protein FUS (2 entities in total)
• Functional Keywords: importin family, transport protein, protein transport-rna binding protein complex, protein transport/rna binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q92973; Nucleus : P35637
• Total number of polymer chains: 2
• Total formula weight: 114308.53

Authors

Yoshizawa, T.,Fung, H.Y.J.,Chook, Y.M. (deposition date: 2017-11-25, release date: 2018-05-16, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.15 Å)