Molecular Architecture of Full-length TRF1 Favors Its Interaction with DNA

J Biol Chem. 2016 Oct 7;291(41):21829-21835. doi: 10.1074/jbc.M116.744896. Epub 2016 Aug 25.

Abstract

Telomeres are specific DNA-protein structures found at both ends of eukaryotic chromosomes that protect the genome from degradation and from being recognized as double-stranded breaks. In vertebrates, telomeres are composed of tandem repeats of the TTAGGG sequence that are bound by a six-subunit complex called shelterin. Molecular mechanisms of telomere functions remain unknown in large part due to lack of structural data on shelterins, shelterin complex, and its interaction with the telomeric DNA repeats. TRF1 is one of the best studied shelterin components; however, the molecular architecture of the full-length protein remains unknown. We have used single-particle electron microscopy to elucidate the structure of TRF1 and its interaction with telomeric DNA sequence. Our results demonstrate that full-length TRF1 presents a molecular architecture that assists its interaction with telometic DNA and at the same time makes TRFH domains accessible to other TRF1 binding partners. Furthermore, our studies suggest hypothetical models on how other proteins as TIN2 and tankyrase contribute to regulate TRF1 function.

Keywords: DNA binding protein; electron microscopy (EM); protein structure; shelterin; telomere; telomeric repeat binding factor1 (TRF1); telomeric repeat-binding factor 1 (TERF1).

MeSH terms

  • Animals
  • DNA / chemistry*
  • DNA / metabolism
  • Mice
  • Protein Domains
  • Sf9 Cells
  • Spodoptera
  • Tandem Repeat Sequences*
  • Tankyrases / chemistry
  • Tankyrases / genetics
  • Tankyrases / metabolism
  • Telomere / chemistry*
  • Telomere / metabolism
  • Telomere-Binding Proteins / chemistry
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism
  • Telomeric Repeat Binding Protein 1 / chemistry*
  • Telomeric Repeat Binding Protein 1 / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism
  • Telomeric Repeat Binding Protein 2 / chemistry
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism

Substances

  • TRF2 protein, mouse
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2
  • Tinf2 protein, mouse
  • DNA
  • Tankyrases
  • Tnks protein, mouse

Associated data

  • PDB/1H6O.pdb
  • PDB/1ITY.pdb
  • PDB/1W0T.pdb
  • PDB/3BQO.pdb
  • PDB/5HKP.pdb