Structural basis of Nrd1-Nab3 heterodimerization

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Chaves-Arquero, Belén
  • dc.contributor.author Martínez-Lumbreras, Santiago
  • dc.contributor.author Camero, Sergio
  • dc.contributor.author Santiveri, Clara M.
  • dc.contributor.author Mirassou, Yasmina
  • dc.contributor.author Campos-Olivas, Ramón
  • dc.contributor.author Jiménez, M. Ángeles
  • dc.contributor.author Calvo, Olga
  • dc.contributor.author Pérez-Cañadillas, José Manuel
  • dc.date.accessioned 2022-04-20T06:30:04Z
  • dc.date.available 2022-04-20T06:30:04Z
  • dc.date.issued 2022
  • dc.description.abstract Heterodimerization of RNA binding proteins Nrd1 and Nab3 is essential to communicate the RNA recognition in the nascent transcript with the Nrd1 recognition of the Ser5-phosphorylated Rbp1 C-terminal domain in RNA polymerase II. The structure of a Nrd1-Nab3 chimera reveals the basis of heterodimerization, filling a missing gap in knowledge of this system. The free form of the Nrd1 interaction domain of Nab3 (NRID) forms a multi-state three-helix bundle that is clamped in a single conformation upon complex formation with the Nab3 interaction domain of Nrd1 (NAID). The latter domain forms two long helices that wrap around NRID, resulting in an extensive protein-protein interface that would explain the highly favorable free energy of heterodimerization. Mutagenesis of some conserved hydrophobic residues involved in the heterodimerization leads to temperature-sensitive phenotypes, revealing the importance of this interaction in yeast cell fitness. The Nrd1-Nab3 structure resembles the previously reported Rna14/Rna15 heterodimer structure, which is part of the poly(A)-dependent termination pathway, suggesting that both machineries use similar structural solutions despite they share little sequence homology and are potentially evolutionary divergent.
  • dc.description.sponsorship NMR experiments were performed in the “Manuel Rico” NMR laboratory (LMR) of the Spanish National Research Council (CSIC), a node of the Spanish Large-Scale National Facility (ICTS R-LRB). Funding was provided by grants: PID2020-112821GB-I00 to JM Pérez-Cañadillas and MÁ Jiménez funded by MCIN/ AEI /10.13039/501100011033/; CTQ2017-84371-P to JM Pérez-Cañadillas and MÁ Jiménez funded by MCIN/ AEI /10.13039/501100011033/ and by “ERDF A way of making Europe”; BFU2017-84694-P to O Calvo funded by MCIN/ AEI /10.13039/501100011033/ and by “ERDF A way of making Europe”; and RED2018-102467-T to O Calvo and JM Pérez-Cañadillas funded by MCIN/ AEI /10.13039/501100011033/. JM Pérez-Cañadillas was also funded by a grant of the Biomedicine program of Community of Madrid (B2017/BMD-3770 RYPSE-CM) that is co-financed with ERDF and ESFESF. The IBFG is supported in part by an institutional grant from the “Junta de Castilla y León” (Programa “Escalera de Excelencia” de la Junta de Castilla y León, Ref. CLU-2017-03 co-funded by O.P. ERDF from Castilla y León 14-20). JM Pérez-Cañadillas would like to thank to Felipe Pozo Lucas for the design and construction of the RYPSE-CM project web page.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Chaves-Arquero B, Martínez-Lumbreras S, Camero S, Santiveri CM, Mirassou Y, Campos-Olivas R, Jiménez MÁ, Calvo O, Pérez-Cañadillas JM. Structural basis of Nrd1-Nab3 heterodimerization. Life Sci Alliance. 2022 Jan 12;5(4):e202101252. DOI: 10.26508/lsa.202101252
  • dc.identifier.doi http://dx.doi.org/10.26508/lsa.202101252
  • dc.identifier.issn 2575-1077
  • dc.identifier.uri http://hdl.handle.net/10230/52850
  • dc.language.iso eng
  • dc.publisher Life Science Alliance
  • dc.relation.ispartof Life Sci Alliance. 2022 Jan 12;5(4):e202101252
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-112821GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CTQ2017-84371-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-84694-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RED2018-102467-T
  • dc.rights © 2022 Chaves-Arquero et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Structural biology
  • dc.subject.keyword Molecular biology
  • dc.subject.keyword Biophysics
  • dc.title Structural basis of Nrd1-Nab3 heterodimerization
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))