Telomere repeat-binding protein
Arabidopsis thaliana (thale cress)
All the information to build up organisms are encoded in DNA. Bacteria have circular DNA molecules as chromosomes. In contrast, eukaryotes have linear DNA molecules which are tightly packed as chromosomes. With regard to replication, bacteria can easily replicate just same circular DNAs, but eukaryotes have "end-replication" problem, meaning those cannot replicate the ends of DNAs without special helps. The ends of chromosomes called telomeres contain repeated nucleotide sequences that enable the end of chromosomes to be effectively replicated, through organisms as diverse as fungi, plants, and mammals. Those consist of double-stranded tandem repeats of TG-rich short sequence elements that are typically five to eight base-pairs in length, followed by a single-stranded 3'-overhangs that extends to the end of the telomeres.
Maintaining proper length of telomere is related to a cell's life span. When the telomere becomes shorter than a certain critical length, cell dysfunction occurs: chromosome degradation, end-to-end fusion, cell senescence and apoptosis. In yeast and mammalian cells, two proteins, telomerase and telomeric repeat-binding proteins (TRPs) are known to be associated with telomeric DNA regulation. Telomerase is an enzyme that elongates telomeric sequences in DNA by using internal RNA moieties. TRPs are also known to interact with either single-stranded or double-stranded DNA, possibly for regulating telomere length, but detailed mechanisms remain unclear.
This is the structure of double-stranded telomeric DNA binding region of TRP from Arabidposis thaliana (At), determined by nuclear magnetic resonance. In solution, this region is a novel four-helix tetrahedron, rather than the three-helix bundle structure making a helix-turn-helix (HTH) conformation found in yeast and human TRPs. Three helice (H1, H2, and H4) serve as the three ridges, and the other (H3) lies at the base of the tetrahedron. The tertiary structure is stabilized by the hydrophobic core composed of hydrophobic residues of the helices. Similar to other TRPs, AtTRP also uses HTH structure motif to bind to telomeric DNA, and H3 plays a major role in sequence-specific recognition. H4 does not interact directly with telomeric DNA.
Protein Data Bank (PDB)
Sue, S.C. Hsiao, H.H. Chung, B.C. Cheng, Y.H. Hsueh, K.L. Chen, C.M. Ho, C.H. Huang, T.H.; "Solution structure of the Arabidopsis thaliana telomeric repeat-binding protein DNA binding domain: a new fold with an additional C-terminal helix"; J.Mol.Biol.; (2006) 356:72-85 PubMed:16337232.
author: Sachiyo Nomura