Comparison between TRF2 and TRF1 of their telomeric DNA-bound structures and DNA-binding activities

Protein Sci. 2005 Jan;14(1):119-30. doi: 10.1110/ps.04983705.


Mammalian telomeres consist of long tandem arrays of double-stranded telomeric TTAGGG repeats packaged by the telomeric DNA-binding proteins TRF1 and TRF2. Both contain a similar C-terminal Myb domain that mediates sequence-specific binding to telomeric DNA. In a DNA complex of TRF1, only the single Myb-like domain consisting of three helices can bind specifically to double-stranded telomeric DNA. TRF2 also binds to double-stranded telomeric DNA. Although the DNA binding mode of TRF2 is likely identical to that of TRF1, TRF2 plays an important role in the t-loop formation that protects the ends of telomeres. Here, to clarify the details of the double-stranded telomeric DNA-binding modes of TRF1 and TRF2, we determined the solution structure of the DNA-binding domain of human TRF2 bound to telomeric DNA; it consists of three helices, and like TRF1, the third helix recognizes TAGGG sequence in the major groove of DNA with the N-terminal arm locating in the minor groove. However, small but significant differences are observed; in contrast to the minor groove recognition of TRF1, in which an arginine residue recognizes the TT sequence, a lysine residue of TRF2 interacts with the TT part. We examined the telomeric DNA-binding activities of both DNA-binding domains of TRF1 and TRF2 and found that TRF1 binds more strongly than TRF2. Based on the structural differences of both domains, we created several mutants of the DNA-binding domain of TRF2 with stronger binding activities compared to the wild-type TRF2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / chemistry*
  • DNA / metabolism
  • Humans
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Protein Structure, Tertiary
  • Telomere / chemistry*
  • Telomere / metabolism
  • Telomeric Repeat Binding Protein 1 / chemistry*
  • Telomeric Repeat Binding Protein 1 / metabolism
  • Telomeric Repeat Binding Protein 2 / chemistry*
  • Telomeric Repeat Binding Protein 2 / metabolism


  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2
  • DNA

Associated data

  • PDB/1VF9
  • PDB/1VFC