Lei Ming, Podell Elaine R, Cech Thomas R
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
Nat Struct Mol Biol. 2004 Dec;11(12):1223-9. doi: 10.1038/nsmb867. Epub 2004 Nov 21.
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.
端粒保护蛋白1（POT1）可与多种真核生物染色体末端的单链悬突相结合。在裂殖酵母粟酒裂殖酵母中，它对染色体末端保护至关重要，并且参与人类细胞中端粒长度的调控。在此，我们报道了人源POT1（hPOT1）蛋白N端一半与端粒单链DNA（ssDNA）十聚体TTAGGGTTAG结合的晶体结构，分辨率为1.73 Å，TTAGGGTTAG是体外结合试验显示的最小紧密结合序列。该结构表明，hPOT1包含两个寡核苷酸/寡糖结合（OB）折叠；N端OB折叠结合前六个核苷酸，类似于粟酒裂殖酵母Pot1pN-ssDNA复合物的结构，而第二个OB折叠结合并保护ssDNA的3'端。这些结果为染色体末端加帽提供了一个原子分辨率模型。
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