Structural basis for substrate recognition and dissociation by human transportin 1

Mol Cell. 2007 Oct 12;28(1):57-67. doi: 10.1016/j.molcel.2007.08.006.


Transportin 1 (Trn1) is a transport receptor that transports substrates from the cytoplasm to the nucleus through nuclear pore complexes by recognizing nuclear localization signals (NLSs). Here we describe four crystal structures of human Trn1 in a substrate-free form as well as in the complex with three NLSs (hnRNP D, JKTBP, and TAP, respectively). Our data have revealed that (1) Trn1 has two sites for binding NLSs, one with high affinity (site A) and one with low affinity (site B), and NLS interaction at site B controls overall binding affinity for Trn1; (2) Trn1 recognizes the NLSs at site A followed by conformational change at site B to interact with the NLSs; and (3) a long flexible loop, characteristic of Trn1, interacts with site B, thereby displacing transport substrate in the nucleus. These studies provide deep understanding of substrate recognition and dissociation by Trn1 in import pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Active Transport, Cell Nucleus / physiology
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Heterogeneous-Nuclear Ribonucleoprotein D / chemistry
  • Heterogeneous-Nuclear Ribonucleoprotein D / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein D / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Localization Signals / genetics
  • Protein Structure, Tertiary*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Sequence Alignment
  • Substrate Specificity
  • beta Karyopherins / chemistry*
  • beta Karyopherins / genetics
  • beta Karyopherins / metabolism*


  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • HNRPDL protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Nuclear Localization Signals
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • TAP1 protein, human
  • TNPO1 protein, human
  • beta Karyopherins

Associated data

  • PDB/2Z5J
  • PDB/2Z5K
  • PDB/2Z5N
  • PDB/2Z5O