5USN

Crystal Structure of Schizosaccharomyces pombe Pot1pC bound to ssRNA/ssDNA chimera (rGrGrUTACGGT)

Summary for 5USN

• Entry DOI: 10.2210/pdb5usn/pdb
• Related: 5USB 5USO
• Descriptor: Protection of telomeres protein 1, 1-3R_9mer DNA/RNA (5'-R(*GP*GP*U)-D(P*TP*AP*CP*GP*GP*T)-3'), SODIUM ION, ... (4 entities in total)
• Functional Keywords: telomeres, ob-fold, dna binding, dna binding protein-dna-rna complex, dna binding protein/dna/rna
• Biological source: Schizosaccharomyces pombe (Fission yeast); More
• Cellular location: Nucleus: O13988
• Total number of polymer chains: 2
• Total formula weight: 19807.94

Authors

Lloyd, N.R.,Wuttke, D.S. (deposition date: 2017-02-13, release date: 2018-04-18, Last modification date: 2023-10-04)

Primary citation

Lloyd, N.R.,Wuttke, D.S.
Discrimination against RNA Backbones by a ssDNA Binding Protein.
Structure, 26:722-733.e2, 2018

PubMed Abstract: Pot1 is the shelterin component responsible for the protection of the single-stranded DNA (ssDNA) overhang at telomeres in nearly all eukaryotic organisms. The C-terminal domain of the DNA-binding domain, Pot1pC, exhibits non-specific ssDNA recognition, achieved through thermodynamically equivalent alternative binding conformations. Given this flexibility, it is unclear how specificity for ssDNA over RNA, an activity required for biological function, is achieved. Examination of the ribose-position specificity of Pot1pC shows that ssDNA specificity is additive but not uniformly distributed across the ligand. High-resolution structures of several Pot1pC complexes with RNA-DNA chimeric ligands reveal Pot1pC discriminates against RNA by utilizing non-compensatory binding modes that feature significant rearrangement of the binding interface. These alternative conformations, accessed through both ligand and protein flexibility, recover much, but not all, of the binding energy, leading to the observed reduction in affinities. These findings suggest that intermolecular interfaces are remarkably sophisticated in their tuning of specificity toward flexible ligands.

PubMed: 29681468
DOI: 10.1016/j.str.2018.03.016

Experimental method

X-RAY DIFFRACTION (1.9 Å)