Structural highlights
Function
POT1_SCHPO Single-stranded telomeric DNA-binding protein that is required to protect the 3'-end telomeric overhang. It binds the consensus sequence 5'-GGTTAC-3'. Regulates telomerase and telomere length.[1] [2] [3]
Publication Abstract from PubMed
Pot1 is the protein responsible for binding to and protecting the 3' single-stranded DNA (ssDNA) overhang at most eukaryotic telomeres. Here, we present the crystal structure of one of the two oligonucleotide/oligosaccharide-binding folds (Pot1pC) that make up the ssDNA-binding domain in S. pombe Pot1. Comparison with the homologous human domain reveals unexpected structural divergence in the mode of ligand binding that explains the differing ligand requirements between species. Despite the presence of apparently base-specific hydrogen bonds, Pot1pC is able to bind a wide range of ssDNA sequences with thermodynamic equivalence. To address how Pot1pC binds ssDNA with little to no specificity, multiple structures of Pot1pC bound to noncognate ssDNA ligands were solved. These structures reveal that this promiscuity is implemented through new binding modes that thermodynamically compensate for base-substitutions through alternate stacking interactions and new H-bonding networks.
Nonspecific Recognition Is Achieved in Pot1pC through the Use of Multiple Binding Modes.,Dickey TH, McKercher MA, Wuttke DS Structure. 2012 Nov 28. pii: S0969-2126(12)00411-X. doi:, 10.1016/j.str.2012.10.015. PMID:23201273[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baumann P, Cech TR. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science. 2001 May 11;292(5519):1171-5. PMID:11349150 doi:http://dx.doi.org/10.1126/science.1060036
- ↑ Lei M, Baumann P, Cech TR. Cooperative binding of single-stranded telomeric DNA by the Pot1 protein of Schizosaccharomyces pombe. Biochemistry. 2002 Dec 10;41(49):14560-8. PMID:12463756
- ↑ Miyoshi T, Kanoh J, Saito M, Ishikawa F. Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. Science. 2008 Jun 6;320(5881):1341-4. doi: 10.1126/science.1154819. PMID:18535244 doi:http://dx.doi.org/10.1126/science.1154819
- ↑ Dickey TH, McKercher MA, Wuttke DS. Nonspecific Recognition Is Achieved in Pot1pC through the Use of Multiple Binding Modes. Structure. 2012 Nov 28. pii: S0969-2126(12)00411-X. doi:, 10.1016/j.str.2012.10.015. PMID:23201273 doi:http://dx.doi.org/10.1016/j.str.2012.10.015
