5UN7

Structure of the human POT1-TPP1 telomeric complex

Summary for 5UN7

• Entry DOI: 10.2210/pdb5un7/pdb
• Descriptor: Protection of telomeres protein 1, Adrenocortical dysplasia protein homolog, ZINC ION, ... (5 entities in total)
• Functional Keywords: telomeric dna binding complex, maintains telomere integrity, dna binding protein, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 44164.97

Authors

Rice, C.,Doukov, T.,Skordalakes, E. (deposition date: 2017-01-30, release date: 2017-04-12, Last modification date: 2024-03-06)

Primary citation

Rice, C.,Shastrula, P.K.,Kossenkov, A.V.,Hills, R.,Baird, D.M.,Showe, L.C.,Doukov, T.,Janicki, S.,Skordalakes, E.
Structural and functional analysis of the human POT1-TPP1 telomeric complex.
Nat Commun, 8:14928-14928, 2017

PubMed Abstract: POT1 and TPP1 are part of the shelterin complex and are essential for telomere length regulation and maintenance. Naturally occurring mutations of the telomeric POT1-TPP1 complex are implicated in familial glioma, melanoma and chronic lymphocytic leukaemia. Here we report the atomic structure of the interacting portion of the human telomeric POT1-TPP1 complex and suggest how several of these mutations contribute to malignant cancer. The POT1 C-terminus (POT1C) forms a bilobal structure consisting of an OB-fold and a holiday junction resolvase domain. TPP1 consists of several loops and helices involved in extensive interactions with POT1C. Biochemical data shows that several of the cancer-associated mutations, partially disrupt the POT1-TPP1 complex, which affects its ability to bind telomeric DNA efficiently. A defective POT1-TPP1 complex leads to longer and fragile telomeres, which in turn promotes genomic instability and cancer.

PubMed: 28393830
DOI: 10.1038/ncomms14928

Experimental method

X-RAY DIFFRACTION (2.1 Å)