@article {Chaves-Arqueroe202101252, author = {Bel{\'e}n Chaves-Arquero and Santiago Mart{\'\i}nez-Lumbreras and Sergio Camero and Clara M Santiveri and Yasmina Mirassou and Ram{\'o}n Campos-Olivas and Maria {\'A}ngeles Jim{\'e}nez and Olga Calvo and Jos{\'e} Manuel P{\'e}rez-Ca{\~n}adillas}, title = {Structural basis of Nrd1{\textendash}Nab3 heterodimerization}, volume = {5}, number = {4}, elocation-id = {e202101252}, year = {2022}, doi = {10.26508/lsa.202101252}, publisher = {Life Science Alliance}, 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{\textendash}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{\textendash}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{\textendash}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.}, URL = {https://www.life-science-alliance.org/content/5/4/e202101252}, eprint = {https://www.life-science-alliance.org/content/5/4/e202101252.full.pdf}, journal = {Life Science Alliance} }