Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity
| Autor: | Javier Coloma, Nayim Gonzalez-Rodriguez, Francisco A Balaguer, Karolina Gmurczyk, Clara Aicart-Ramos, Óscar M Nuero, Juan Román Luque-Ortega, Kimberly Calugaru, Neal F Lue, Fernando Moreno-Herrero, Oscar Llorca |
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| Přispěvatelé: | Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, Instituto de Salud Carlos III, Boehringer Ingelheim Fonds, National Institutes of Health (US), European Commission |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Popis: | The CST complex is a key player in telomere replication and stability, which in yeast comprises Cdc13, Stn1 and Ten1. While Stn1 and Ten1 are very well conserved across species, Cdc13 does not resemble its mammalian counterpart CTC1 either in sequence or domain organization, and Cdc13 but not CTC1 displays functions independently of the rest of CST. Whereas the structures of human CTC1 and CST have been determined, the molecular organization of Cdc13 remains poorly understood. Here, we dissect the molecular architecture of Candida glabrata Cdc13 and show how it regulates binding to telomeric sequences. Cdc13 forms dimers through the interaction between OB-fold 2 (OB2) domains. Dimerization stimulates binding of OB3 to telomeric sequences, resulting in the unfolding of ssDNA secondary structure. Once bound to DNA, Cdc13 prevents the refolding of ssDNA by mechanisms involving all domains. OB1 also oligomerizes, inducing higher-order complexes of Cdc13 in vitro. OB1 truncation disrupts these complexes, affects ssDNA unfolding and reduces telomere length in C. glabrata. Together, our results reveal the molecular organization of C. glabrata Cdc13 and how this regulates the binding and the structure of DNA, and suggest that yeast species evolved distinct architectures of Cdc13 that share some common principles. Agencia Estatal de Investigacion [AEI/10.13039/5011000 ´ 11 033]; Ministerio de Ciencia e Innovacion, and co-´ funded by the European Regional Development Fund(ERDF-UE) [PID2020-114429RB-I00 to O.L., PID2020-112998GB-100 to F.M.-H]; Autonomous Region of Madrid and co-funded by the European Social Fund and the European Regional Development Fund [Y2018/BIO4747 and P2018/NMT4443 to O.L. and F.M.-H.]; National Institute of Health Carlos III to CNIO; J.R.L.O. and O.N. acknowledge support from the Molecular Interactions Facility at the CIB-CSIC; N.G.-R. was supported by a Boehringer Ingelheim Fonds PhD fellowship; N.F.L. is funded by NIH [GM107287]. Funding for open access charge: Agencia Estatal de Investigacion [AEI ´ /10.13039/501100011 033]; Ministerio de Ciencia e Innovacion, co-funded by the Eu-ropean Regional Development Fund (ERDF) [PID2020-114429RB-I00]. |
| Databáze: | OpenAIRE |
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