Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection.
The POT1 (protection of telomeres 1) protein binds the single-stranded overhang at the ends of chromosomes in diverse eukaryotes. It is essential for chromosome end-protection in the fission yeast Schizosaccharomyces pombe, and it is involved in regulation of telomere length in human cells. Here, we report the crystal structure at a resolution of 1.73 A of the N-terminal half of human POT1 (hPOT1) protein bound to a telomeric single-stranded DNA (ssDNA) decamer, TTAGGGTTAG, the minimum tight-binding sequence indicated by in vitro binding assays. The structure reveals that hPOT1 contains two oligonucleotide/ oligosaccharide-binding (OB) folds; the N-terminal OB fold binds the first six nucleotides, resembling the structure of the S. pombe Pot1pN-ssDNA complex, whereas the second OB fold binds and protects the 3' end of the ssDNA. These results provide an atomic-resolution model for chromosome end-capping.
Lei
Ming
M
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
Podell
Elaine R
ER
Cech
Thomas R
TR
D001483:Base Sequence; D018360:Crystallography, X-Ray; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*
D004277:DNA, Single-Stranded; C440849:POT1 protein, human; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C499082:pot1 protein, S pombe; D019098:Telomerase