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TitleStructural basis of telomeric nucleosome recognition by shelterin factor TRF1.
Journal, issue, pagesSci Adv, Vol. 9, Issue 34, Page eadi4148, Year 2023
Publish dateAug 25, 2023
AuthorsHongmiao Hu / Anne-Marie M van Roon / George E Ghanim / Bilal Ahsan / Abraham O Oluwole / Sew-Yeu Peak-Chew / Carol V Robinson / Thi Hoang Duong Nguyen /
PubMed AbstractShelterin and nucleosomes are the key players that organize mammalian chromosome ends into the protective telomere caps. However, how they interact with each other at telomeres remains unknown. We ...Shelterin and nucleosomes are the key players that organize mammalian chromosome ends into the protective telomere caps. However, how they interact with each other at telomeres remains unknown. We report cryo-electron microscopy structures of a human telomeric nucleosome both unbound and bound to the shelterin factor TRF1. Our structures reveal that TRF1 binds unwrapped nucleosomal DNA ends by engaging both the nucleosomal DNA and the histone octamer. Unexpectedly, TRF1 binding shifts the register of the nucleosomal DNA by 1 bp. We discovered that phosphorylation of the TRF1 C terminus and a noncanomical DNA binding surface on TRF1 are critical for its association with telomeric nucleosomes. These insights into shelterin-chromatin interactions have crucial implications for understanding telomeric chromatin organization and other roles of shelterin at telomeres including replication and transcription.
External linksSci Adv / PubMed:37624885 / PubMed Central
MethodsEM (single particle)
Resolution2.52 - 6.67 Å
Structure data

17251

8ox0

EMDB-17251, PDB-8ox0:
Structure of apo telomeric nucleosome
Method: EM (single particle) / Resolution: 2.52 Å

17252

8ox1

EMDB-17252, PDB-8ox1:
Structure of TRF1core in complex with telomeric nucleosome
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-17253: Structure of TRF1core in complex with telomeric nucleosome (4:1 complex)
Method: EM (single particle) / Resolution: 6.67 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsDNA BINDING PROTEIN / Telomeric nucleosome / shelterin / telomere

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