Surface Properties Determining Passage Rates of Proteins through Nuclear Pores
2018 | journal article; research paper
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- Authors
- Frey, Steffen; Rees, Renate; Schünemann, Jürgen; Ng, Sheung Chun; Fünfgeld, Kevser; Huyton, Trevor; Görlich, Dirk
- 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.
- Issue Date
- 2018
- Journal
- Cell
- Project
- SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente
SFB 1190 | P08: Kernporenpassage großer, makromolekularer Komplexe, wie beispielsweise ribosomaler Untereinheiten - Working Group
- RG Görlich (Cellular Logistics)
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English