Molecular basis for the recognition of snurportin 1 by importin beta

J Biol Chem. 2008 Mar 21;283(12):7877-84. doi: 10.1074/jbc.M709093200. Epub 2008 Jan 9.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Cell Nucleus / metabolism
  • Humans
  • Nuclear Pore Complex Proteins / chemistry
  • Nuclear Pore Complex Proteins / metabolism
  • Protein Binding / physiology
  • RNA Cap-Binding Proteins / chemistry*
  • RNA Cap-Binding Proteins / metabolism
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Structure-Activity Relationship
  • beta Karyopherins / chemistry*
  • beta Karyopherins / metabolism

Substances

  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • RNA Cap-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • SNUPN protein, human
  • beta Karyopherins

Associated data

  • PDB/UNKNOWN