title: Quantitative structural analysis of importin-β flexibility: paradigm for solenoid protein structures.
abstract: The structure of solenoid proteins facilitates a higher degree of flexibility than most folded proteins. In importin-β, a nuclear import factor built from 19 tandem HEAT repeats, flexibility plays a crucial role in allowing interactions with a range of different partners. We present a comprehensive analysis of importin-β flexibility based on a number of different approaches. We determined the crystal structure of unliganded Saccharomyces cerevisiae importin-β (Kap95) to allow a quantitative comparison with importin-β bound to different partners. Complementary mutagenesis, small angle X-ray scattering and molecular dynamics studies suggest that the protein samples several conformations in solution. The analyses suggest the flexibility of the solenoid is generated by cumulative small movements along its length. Importin-β illustrates how solenoid proteins can orchestrate protein interactions in many cellular pathways.
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales 2650, Australia. jforwood@csu.edu.au
authors.forename: Jade K
authors.initials: JK
authors.lastname: Forwood
authors.forename: Allison
authors.initials: A
authors.lastname: Lange
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zachariae
authors.forename: Mary
authors.initials: M
authors.lastname: Marfori
authors.forename: Callie
authors.initials: C
authors.lastname: Preast
authors.forename: Helmut
authors.initials: H
authors.lastname: Grubmüller
authors.forename: Murray
authors.initials: M
authors.lastname: Stewart
authors.forename: Anita H
authors.initials: AH
authors.lastname: Corbett
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D028961:beta Karyopherins