Chaves-Arquero, BelénMartínez-Lumbreras, SantiagoCamero, SergioSantiveri, Clara M.Mirassou, YasminaCampos-Olivas, RamónJiménez, M. ÁngelesCalvo, OlgaPérez-Cañadillas, José Manuel2022-04-202022-04-202022Chaves-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.2021012522575-1077http://hdl.handle.net/10230/52850Heterodimerization 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.application/pdfeng© 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/).Structural basis of Nrd1-Nab3 heterodimerizationinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.26508/lsa.202101252Structural biologyMolecular biologyBiophysicsinfo:eu-repo/semantics/openAccess