Surface Properties Determining Passage Rates of Proteins through Nuclear Pores - PubMed (original) (raw)

. 2018 Jun 28;174(1):202-217.e9.

doi: 10.1016/j.cell.2018.05.045.

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Surface Properties Determining Passage Rates of Proteins through Nuclear Pores

Steffen Frey et al. Cell. 2018.

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Abstract

Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport through an FG domain-controlled barrier. We now explore how surface-features of a mobile species determine its NPC passage rate. Negative charges and lysines impede passage. Hydrophobic residues, certain polar residues (Cys, His), and, surprisingly, charged arginines have striking translocation-promoting effects. Favorable cation-π interactions between arginines and FG-phenylalanines may explain this apparent paradox. Application of these principles to redesign the surface of GFP resulted in variants that show a wide span of transit rates, ranging from 35-fold slower than wild-type to ∼500 times faster, with the latter outpacing even naturally occurring nuclear transport receptors (NTRs). The structure of a fast and particularly FG-specific GFPNTR variant illustrates how NTRs can expose multiple regions for binding hydrophobic FG motifs while evading non-specific aggregation. Finally, we document that even for NTR-mediated transport, the surface-properties of the "passively carried" cargo can strikingly affect the translocation rate.

Keywords: NTF2; aggregation; cargo; exportin; hydrogel; importin; nuclear pore complex; permeability barrier; phase separation; protein homeostasis.

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