Insights into POT1 structural dynamics revealed by cryo-EM.
Publication Date
2022Journal Title
PLoS One
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Volume
17
Issue
2
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Smith, E. W., Lattmann, S., Liu, Z. B., Ahsan, B., & Rhodes, D. (2022). Insights into POT1 structural dynamics revealed by cryo-EM.. PLoS One, 17 (2) https://doi.org/10.1371/journal.pone.0264073
Abstract
Telomeres are protein-DNA complexes that protect the ends of linear eukaryotic chromosomes. Mammalian telomeric DNA consists of 5'-(TTAGGG)n-3' double-stranded repeats, followed by up to several hundred bases of a 3' single-stranded G-rich overhang. The G-rich overhang is bound by the shelterin component POT1 which interacts with TPP1, the component involved in telomerase recruitment. A previously published crystal structure of the POT1 N-terminal half bound to the high affinity telomeric ligand 5'-TTAGGGTTAG-3' showed that the first six nucleotides, TTAGGG, are bound by the OB1 fold, while the adjacent OB2 binds the last four, TTAG. Here, we report two cryo-EM structures of full-length POT1 bound by the POT1-binding domain of TPP1. The structures differ in the relative orientation of the POT1 OB1 and OB2, suggesting that these two DNA-binding OB folds take up alternative conformations. Supporting DNA binding studies using telomeric ligands in which the OB1 and OB2 binding sites were spaced apart, show that POT1 binds with similar affinities to spaced or contiguous binding sites, suggesting plasticity in DNA binding and a role for the alternative conformations observed. A likely explanation is that the structural flexibility of POT1 enhances binding to the tandemly arranged telomeric repeats and hence increases telomere protection.
Keywords
Research Article, Physical sciences, Research and analysis methods, Biology and life sciences
Sponsorship
Singapore Ministry of Education Academic Research Fund (AcRF) Tier 3 (MOE2012-T3-1-001)
Identifiers
pone-d-21-36536
External DOI: https://doi.org/10.1371/journal.pone.0264073
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334164
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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