Karyopherin-β2 Recognition of a PY-NLS Variant that Lacks the Proline-Tyrosine Motif.
Karyopherin-β2 or Transportin-1 binds proline-tyrosine nuclear localization signals (PY-NLSs) in its cargos. PY-NLSs are described by structural disorder, overall positive charge, and binding epitopes composed of an N-terminal hydrophobic or basic motif and a C-terminal R-X2-5P-Y motif. The N-terminal tail of histone H3 binds Kapβ2 with high affinity but does not contain a recognizable PY-NLS. The crystal structure of the Kapβ2-H3 tail shows residues 11-27 of H3 binding to the PY-NLS site of Kapβ2. H3 residues11TGGKAPRK18bind the site for PY-NLS Epitope 1 (N-terminal hydrophobic/basic motif), which is most important for Kapβ2-binding. H3 residue Arg26 occupies the PY-NLS Epitope 2 position (usually arginine of R-X2-5P-Y) but PY-NLS Epitope 3 (proline-tyrosine motif) is missing in the H3 tail. Histone H3 thus provides an example of a PY-NLS variant with no proline-tyrosine or homologous proline-hydrophobic motif. The H3 tail uses a very strong Epitope 1 to compensate for loss of the often-conserved proline-tyrosine epitope.
Department of Pharmacology, University of Texas Southwestern, Dallas, TX 75390, USA.
Michael
M
Soniat
Department of Pharmacology, University of Texas Southwestern, Dallas, TX 75390, USA. Electronic address: yuhmin.chook@utsouthwestern.edu.
Yuh Min
YM
Chook
D020816:Amino Acid Motifs; D001665:Binding Sites; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D019913:Nuclear Localization Signals / Q000235:genetics*; D011392:Proline / Q000235:genetics; D011485:Protein Binding; D000072417:Protein Domains; D014443:Tyrosine / Q000235:genetics; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism*
D000939:Epitopes; D006657:Histones; D019913:Nuclear Localization Signals; C108121:TNPO1 protein, human; D028961:beta Karyopherins; D014443:Tyrosine; D011392:Proline
PY-NLS; histones; importin; karyopherin; nuclear import; nuclear localization signal, NLS