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TitleCryo-EM structure of substrate-bound human telomerase holoenzyme.
Journal, issue, pagesNature, Vol. 557, Issue 7704, Page 190-195, Year 2018
Publish dateApr 25, 2018
AuthorsThi Hoang Duong Nguyen / Jane Tam / Robert A Wu / Basil J Greber / Daniel Toso / Eva Nogales / Kathleen Collins /
PubMed AbstractThe enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, ...The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, and ageing, but progress towards clinical manipulation of telomerase has been hampered by the lack of structural data. Here we present the cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme at subnanometre resolution, showing two flexibly RNA-tethered lobes: the catalytic core with telomerase reverse transcriptase (TERT) and conserved motifs of telomerase RNA (hTR), and an H/ACA ribonucleoprotein (RNP). In the catalytic core, RNA encircles TERT, adopting a well-ordered tertiary structure with surprisingly limited protein-RNA interactions. The H/ACA RNP lobe comprises two sets of heterotetrameric H/ACA proteins and one Cajal body protein, TCAB1, representing a pioneering structure of a large eukaryotic family of ribosome and spliceosome biogenesis factors. Our findings provide a structural framework for understanding human telomerase disease mutations and represent an important step towards telomerase-related clinical therapeutics.
External linksNature / PubMed:29695869 / PubMed Central
MethodsEM (single particle)
Resolution7.7 - 10.2 Å
Structure data

EMDB-7518:
The catalytic core of the cryo-EM structure of substrate-bound human telomerase holoenzyme
Method: EM (single particle) / Resolution: 7.7 Å

EMDB-7519:
The H/ACA ribonucleoprotein lobe of the cryo-EM structure of substrate-bound human telomerase holoenzyme
Method: EM (single particle) / Resolution: 8.2 Å

EMDB-7521:
The overall reconstruction of human telomerase holoenzyme
Method: EM (single particle) / Resolution: 10.2 Å

Source
  • Homo sapiens (human)

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