Prolines in the α-helix confer the structural flexibility and functional integrity of importin-β

• Published in: Journal of cell science Vol. 131; no. 1; p. jcs206326
• Main Authors: Kumeta, Masahiro, Konishi, Hide A, Zhang, Wanzhen, Sakagami, Sayuri, Yoshimura, Shige H
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.01.2018
• Subjects: Active Transport, Cell Nucleus - genetics; Alanine; beta Karyopherins - chemistry; beta Karyopherins - genetics; Flexibility; Helices; Humans; Hydrophobicity; Integrity; Models, Molecular; Mutation; Nuclear Pore - genetics; Nuclear Pore - metabolism; Nuclear transport; Proline - chemistry; Protein Conformation, alpha-Helical; ran GTP-Binding Protein - metabolism; Receptors; Structure-function relationships; Transport; Proline; Molecular flexibility; Karyopherin; Molecular structure; Nuclear transport; Importin
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.206326

The karyopherin family of nuclear transport receptors is composed of a long array of amphiphilic α-helices and undergoes flexible conformational changes to pass through the hydrophobic crowding barrier of the nuclear pore. Here, we focused on the characteristic enrichment of prolines in the middle of the outer α-helices of importin-β. When these prolines were substituted with alanine, nuclear transport activity was reduced drastically and , and caused a severe defect in mitotic progression. These mutations did not alter the overall folding of the helical repeat or affect its interaction with cargo or the regulatory factor Ran. However, and analyses revealed that the mutant lost structural flexibility and could not undergo rapid conformational changes when transferring from a hydrophilic to hydrophobic environment or vice versa. These findings reveal the essential roles of prolines in ensuring the structural flexibility and functional integrity of karyopherins.