Figure 1.

(A) Known properties of the conserved TRFH domains in shelterin complexes. Of note, TRFHs do not exhibit this full set of properties. For instance, TIN2 seems devoid of DNA binding. (B) A schematic tree depicting the phylogenetic relationships of most eukaryotes into six major supergroups (underlined)¹¹. The proteins in red contain a TRFH whose structure was solved, the proteins in green are TRFH protein candidates on the basis of a TRF-like domain organization, i.e., the presence of a telobox at their C-terminus. Structure determination of various putative TRFH in distantly related shelterin proteins should shed light on whether TRFH occurred at the very beginning or even before the expansion of the eukaryotic tree of life.