2I46

Crystal structure of human TPP1

2I46 の概要

• エントリーDOI: 10.2210/pdb2i46/pdb
• 分子名称: Adrenocortical dysplasia protein homolog (2 entities in total)
• 機能のキーワード: tpp1, ob fold, pot1 binding, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q96AP0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35117.07

構造登録者

Wang, F.,Podell, E.R.,Zaug, A.J.,Yang, Y.T.,Baciu, P.,Else, T.,Hammer, G.D.,Cech, T.R.,Lei, M. (登録日: 2006-08-21, 公開日: 2006-11-28, 最終更新日: 2024-02-21)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)