title: Molecular basis for the recognition of snurportin 1 by importin beta.
abstract: The nuclear import of uridine-rich ribonucleoproteins is mediated by the transport adaptor snurportin 1 (SNP1). Similar to importin alpha, SNP1 uses an N-terminal importin beta binding (sIBB) domain to recruit the receptor importin beta and gain access to the nucleus. In this study, we demonstrate that the sIBB domain has a bipartite nature, which contains two distinct binding determinants for importin beta. The first determinant spans residues 25-65 and includes the previously identified importin alpha IBB (alphaIBB) region of homology. The second binding determinant encompasses residues 1-24 and resembles region 1011-1035 of the nucleoporin 153 (Nup153). The two binding determinants synergize within the sIBB domain to confer a low nanomolar binding affinity for importin beta (K(d) approximately 2 nm) in an interaction that, in vitro, is displaced by RanGTP. We propose that in vivo the synergy of Nup153 and nuclear RanGTP promotes translocation of uridine-rich ribonucleoproteins into the nucleus.
authors.affiliation: Department of Biochemistry and Molecular Biology, State University of New York (SUNY) Upstate Medical University, Syracuse, New York 13210, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Mitrousis
authors.forename: Adam S
authors.initials: AS
authors.lastname: Olia
authors.forename: Nancy
authors.initials: N
authors.lastname: Walker-Kopp
authors.forename: Gino
authors.initials: G
authors.lastname: Cingolani
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D039381:RNA Cap-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins; D039381:RNA Cap-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C114090:SNUPN protein, human; D028961:beta Karyopherins