Surface Properties Determining Passage Rates of Proteins through Nuclear Pores.
Cell
; 174(1): 202-217.e9, 2018 06 28.
Article
em En
| MEDLINE
| ID: mdl-29958108
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 â¼500 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Poro Nuclear
/
Transporte Ativo do Núcleo Celular
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Complexo de Proteínas Formadoras de Poros Nucleares
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article