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

• Kumeta, Masahiro

  Graduate School of Biostudies, Kyoto University

• Konishi, Hide A.

  Graduate School of Biostudies, Kyoto University

• Zhang, Wanzhen

  Graduate School of Biostudies, Kyoto University

• Sakagami, Sayuri

  Graduate School of Biostudies, Kyoto University

• Yoshimura, Shige H.

  Graduate School of Biostudies, Kyoto University

Abstract

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 in vivo and in vitro, 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, in vitro and in silico 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.

Journal

• Journal of Cell Science

  Journal of Cell Science 131 (1), 2018-01-04

  The Company of Biologists

Keywords

• Importin
• Karyopherin
• Molecular flexibility
• Molecular structure
• Nuclear transport
• Proline

Details

• CRID: 1050845760784781568
• NII Article ID: 120006384169
• ISSN: 00219533
• HANDLE: 2433/229014
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles