Conformational plasticity and allosteric communication networks explain Shelterin protein TPP1 binding to human telomerase.

ABSTRACT: The Shelterin complex protein TPP1 interacts with human telomerase (TERT) by means of the TEL-patch region, controlling telomere homeostasis. Aberrations in the TPP1-TERT heterodimer formation might lead to short telomeres and severe diseases like dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. In the present study, we provide a thorough characterization of the structural properties of the TPP1's OB-domain by combining data coming from microsecond-long molecular dynamics calculations, time-series analyses, and graph-based networks. Our results show that the TEL-patch conformational freedom is influenced by a network of long-range amino acid communications that together determine the proper TPP1-TERT binding. Furthermore, we reveal that in TPP1 pathological variants Glu169Δ, Lys17

SUBMITTER: Aureli S 

PROVIDER: S-EPMC10630336 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature