2I46

Crystal structure of human TPP1

Summary for 2I46

• Entry DOI: 10.2210/pdb2i46/pdb
• Descriptor: Adrenocortical dysplasia protein homolog (2 entities in total)
• Functional Keywords: tpp1, ob fold, pot1 binding, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q96AP0
• Total number of polymer chains: 2
• Total formula weight: 35117.07

Authors

Wang, F.,Podell, E.R.,Zaug, A.J.,Yang, Y.T.,Baciu, P.,Else, T.,Hammer, G.D.,Cech, T.R.,Lei, M. (deposition date: 2006-08-21, release date: 2006-11-28, Last modification date: 2024-02-21)

Primary citation

Wang, F.,Podell, E.R.,Zaug, A.J.,Yang, Y.,Baciu, P.,Cech, T.R.,Lei, M.
The POT1-TPP1 telomere complex is a telomerase processivity factor.
Nature, 445:506-510, 2007

PubMed Abstract: Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 (protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.

PubMed: 17237768
DOI: 10.1038/nature05454

Experimental method

X-RAY DIFFRACTION (2.7 Å)