title: A molecular switch between alternative conformational states in the complex of Ran and importin beta1.
abstract: Several million macromolecules are exchanged each minute between the nucleus and cytoplasm by receptor-mediated transport. Most of this traffic is controlled by the small GTPase Ran, which regulates assembly and disassembly of the receptor-cargo complexes in the appropriate cellular compartment. Here we applied dynamic force spectroscopy to study the interaction of Ran with the nuclear import receptor importin beta1 (impbeta) at the single-molecule level. We found that the complex alternates between two distinct conformational states of different adhesion strength. The application of an external mechanical force shifts equilibrium toward one of these states by decreasing the height of the interstate activation energy barrier. The other state can be stabilized by a functional Ran mutant that increases this barrier. These results support a model whereby functional control of Ran-impbeta is achieved by a population shift between pre-existing alternative conformations.
authors.affiliation: Department of Biological Chemistry, the Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Reinat
authors.initials: R
authors.lastname: Nevo
authors.forename: Cordula
authors.initials: C
authors.lastname: Stroh
authors.forename: Ferry
authors.initials: F
authors.lastname: Kienberger
authors.forename: David
authors.initials: D
authors.lastname: Kaftan
authors.forename: Vlad
authors.initials: V
authors.lastname: Brumfeld
authors.forename: Michael
authors.initials: M
authors.lastname: Elbaum
authors.forename: Ziv
authors.initials: Z
authors.lastname: Reich
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
mesh_terms: D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D011487:Protein Conformation; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000737:chemistry* / Q000378:metabolism
chemical_list: C424166:KPNB1 protein, human; D028961:beta Karyopherins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein