Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2

TRF1 and TRF2 are key components of vertebrate telomeres. They bind to doub le-stranded telomeric DNA as homodimers. Dimerization involves the TRF homo logy (TRFH) domain, which also mediates interactions with other telomeric p roteins. The crystal structures of the dimerization domains from human TRF1 and TRF2 were determined at 2.9 and 2.2 Angstrom resolution, respectively. Despite a modest sequence identity, the two TRFH domains have the same ent irely alpha -helical architecture, resembling a twisted horseshoe. The dime rization interfaces feature unique interactions that prevent heterodimeriza tion. Mutational analysis of TRF1 corroborates the structural data and unde rscores the importance of the TRFH domain in dimerization, DNA binding, and telomere localization. A possible structural homology between the TRFH dom ain of fission yeast telomeric protein Taz1 with those of the vertebrate TR Fs is suggested.