Crystal structure of human Karyopherin β2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2
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Import-Karyopherin or Importin proteins bind nuclear localization signals (NLSs) to mediate the import of proteins into the cell nucleus. Karyopherin β2 or Kapβ2, also known as Transportin, is a member of this transporter family responsible for the import of numerous RNA binding proteins. Kapβ2 recognizes a targeting signal termed the PY-NLS that lies within its cargos to target them through the nuclear pore complex. The recognition of PY-NLS by Kapβ2 is conserved throughout eukaryotes. Kap104, the Kapβ2 homolog in Saccharomyces cerevisiae, recognizes PY-NLSs in cargos Nab2, Hrp1, and Tfg2. We have determined the crystal structure of Kapβ2 bound to the PY-NLS of the mRNA processing protein Nab2 at 3.05-Å resolution. A seven-residue segment of the PY-NLS of Nab2 is observed to bind Kapβ2 in an extended conformation and occupies the same PY-NLS binding site observed in other Kapβ2·PY-NLS structures.
KeywordsKaryopherin Importin Nuclear import Nuclear localization signal Nucleocytoplasmic transport Nuclear pore Nab2
We thank Z. Zhang for advice on protein purification and M. Rout for discussions. This work is funded by the National Institutes of Health U01 GM98256-01 (YMC, ASC), U54 GM094662 (SCA) and R01-GM069909 (YMC), Welch Foundation (I-1532; YMC), Leukemia and Lymphoma Society Scholar award (YMC), CPRIT (RP120352; YMC) and UT Southwestern Endowed Scholars Program (YMC). This publication was made possible by the Center for Synchrotron Biosciences grant, P30-EB-009998, from the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Use of the National Synchrotron Light Source, Brookhaven National Laboratory, was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Basic Energy Sciences. Access to the LRL-CAT beam line facilities at Sector 31 of the APS was provided by Eli Lilly, which operates the facility.
- 4.Lee B, Cansizoglu A, Suel K, Louis T, Zhang Z, Chook Y (2006) Rules for nuclear localization sequence recognition by Karyopherinβ2. Cell 126:544–558Google Scholar
- 16.Davis IW, Leaver-Fay A, Chen VB, Block JN, Kapral GJ, Wang X, Murray LW, Arendall III WB, Snoeyink J, Richardson JS, Richardson DC (2007) MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucl Acids Res 35:W375–W383 (http://molprobity.biochem.duke.edu/)Google Scholar