Open Access

Nature Communications, volume 8, issue 1, publication number 14928

Structural and functional analysis of the human POT1-TPP1 telomeric complex

Rice Cory ^{1, 2}

Shastrula Prashanth Krishna ¹

Kossenkov Andrew V. ¹

Hills Robert ¹

Baird Duncan M ³

Showe Louise C ¹

Doukov Tzanko ⁴

Janicki Susan ¹

Skordalakes Emmanuel ^{1, 2}

Hide authors affiliations Show authors affiliations: 4 affiliations

the Wistar Institute, Philadelphia, USA |

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA |

Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, UK |

⁴

Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, USA |

Publication type: Journal Article

Publication date: 2017-04-10

Springer Nature

Journal: Nature Communications

Quartile SCImago

Quartile WOS

Impact factor: 16.6

ISSN: 20411723

DOI: 10.1038/ncomms14928

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PubMed ID: 28393830

General Chemistry

General Biochemistry, Genetics and Molecular Biology

General Physics and Astronomy

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. POT1 and TTP1 are part of the shelterin complex that caps and stabilizes the ends of telomeres. Here the authors present a structural analysis of the human POT1-TTP1 complex, shedding light on how it assembles and how cancer-associated mutations impact its assembly and function.

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Citations by journals

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Cancers	Cancers, 3, 3.8% Cancers 3 publications, 3.8%
Current Opinion in Structural Biology	Current Opinion in Structural Biology, 3, 3.8% Current Opinion in Structural Biology 3 publications, 3.8%
Journal of Biological Chemistry	Journal of Biological Chemistry, 3, 3.8% Journal of Biological Chemistry 3 publications, 3.8%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 2, 2.53% International Journal of Molecular Sciences 2 publications, 2.53%
Cells	Cells, 2, 2.53% Cells 2 publications, 2.53%
Frontiers in Molecular Biosciences	Frontiers in Molecular Biosciences, 2, 2.53% Frontiers in Molecular Biosciences 2 publications, 2.53%
Nature Communications	Nature Communications, 2, 2.53% Nature Communications 2 publications, 2.53%
Nature	Nature, 2, 2.53% Nature 2 publications, 2.53%
Computational and Structural Biotechnology Journal	Computational and Structural Biotechnology Journal, 2, 2.53% Computational and Structural Biotechnology Journal 2 publications, 2.53%
PLoS ONE	PLoS ONE, 2, 2.53% PLoS ONE 2 publications, 2.53%
Journal of Cellular Physiology	Journal of Cellular Physiology, 2, 2.53% Journal of Cellular Physiology 2 publications, 2.53%
EMBO Journal	EMBO Journal, 2, 2.53% EMBO Journal 2 publications, 2.53%
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Frontiers in Veterinary Science	Frontiers in Veterinary Science, 1, 1.27% Frontiers in Veterinary Science 1 publication, 1.27%
Photochemical and Photobiological Sciences	Photochemical and Photobiological Sciences, 1, 1.27% Photochemical and Photobiological Sciences 1 publication, 1.27%
Cell Research	Cell Research, 1, 1.27% Cell Research 1 publication, 1.27%
Cellular and Molecular Life Sciences	Cellular and Molecular Life Sciences, 1, 1.27% Cellular and Molecular Life Sciences 1 publication, 1.27%
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Structure	Structure, 1, 1.27% Structure 1 publication, 1.27%
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Elsevier	Elsevier, 18, 22.78% Elsevier 18 publications, 22.78%
Springer Nature	Springer Nature, 11, 13.92% Springer Nature 11 publications, 13.92%
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Public Library of Science (PLoS)	Public Library of Science (PLoS), 3, 3.8% Public Library of Science (PLoS) 3 publications, 3.8%
American Society for Biochemistry and Molecular Biology	American Society for Biochemistry and Molecular Biology, 3, 3.8% American Society for Biochemistry and Molecular Biology 3 publications, 3.8%
Wiley	Wiley, 3, 3.8% Wiley 3 publications, 3.8%
Taylor & Francis	Taylor & Francis, 2, 2.53% Taylor & Francis 2 publications, 2.53%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 2, 2.53% American Association for the Advancement of Science (AAAS) 2 publications, 2.53%
EMBO press	EMBO press, 2, 2.53% EMBO press 2 publications, 2.53%
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American Society for Clinical Investigation	American Society for Clinical Investigation, 1, 1.27% American Society for Clinical Investigation 1 publication, 1.27%
Bentham Science	Bentham Science, 1, 1.27% Bentham Science 1 publication, 1.27%
Wolters Kluwer Health	Wolters Kluwer Health, 1, 1.27% Wolters Kluwer Health 1 publication, 1.27%
American Chemical Society (ACS)	American Chemical Society (ACS), 1, 1.27% American Chemical Society (ACS) 1 publication, 1.27%
Dove Medical Press	Dove Medical Press, 1, 1.27% Dove Medical Press 1 publication, 1.27%
Walter de Gruyter	Walter de Gruyter, 1, 1.27% Walter de Gruyter 1 publication, 1.27%
American Association for Cancer Research (AACR)	American Association for Cancer Research (AACR), 1, 1.27% American Association for Cancer Research (AACR) 1 publication, 1.27%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 1, 1.27% Proceedings of the National Academy of Sciences (PNAS) 1 publication, 1.27%
Annual Reviews	Annual Reviews, 1, 1.27% Annual Reviews 1 publication, 1.27%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 1, 1.27% Cold Spring Harbor Laboratory 1 publication, 1.27%
BMJ	BMJ, 1, 1.27% BMJ 1 publication, 1.27%
	2 4 6 8 10 12 14 16 18

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Rice C. et al. Structural and functional analysis of the human POT1-TPP1 telomeric complex // Nature Communications. 2017. Vol. 8. No. 1. 14928

GOST all authors (up to 50) Copy

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 // Nature Communications. 2017. Vol. 8. No. 1. 14928

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/ncomms14928

UR - https://doi.org/10.1038%2Fncomms14928

TI - Structural and functional analysis of the human POT1-TPP1 telomeric complex

T2 - Nature Communications

AU - Rice, Cory

AU - Shastrula, Prashanth Krishna

AU - Kossenkov, Andrew V.

AU - Hills, Robert

AU - Baird, Duncan M

AU - Showe, Louise C

AU - Doukov, Tzanko

AU - Janicki, Susan

AU - Skordalakes, Emmanuel

PY - 2017

DA - 2017/04/10 00:00:00

PB - Springer Nature

IS - 1

VL - 8

PMID - 28393830

SN - 2041-1723

ER -

BibTex

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BibTex Copy

@article{2017_Rice,

author = {Cory Rice and Prashanth Krishna Shastrula and Andrew V. Kossenkov and Robert Hills and Duncan M Baird and Louise C Showe and Tzanko Doukov and Susan Janicki and Emmanuel Skordalakes},

title = {Structural and functional analysis of the human POT1-TPP1 telomeric complex},

journal = {Nature Communications},

year = {2017},

volume = {8},

publisher = {Springer Nature},

month = {apr},

url = {https://doi.org/10.1038%2Fncomms14928},

number = {1},

doi = {10.1038/ncomms14928}

}

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Publisher

Springer Nature

Journal

Nature Communications

Quartile SCImago

Quartile WOS

Impact factor

16.6

ISSN

20411723 (Print)