The structure of erb1-Ytm1 complex reveals the functional importance of a high-Affinity binding between two β-Propellers during the assembly of large ribosomal subunits in eukaryotes.
Authors
M.Wegrecki,
O.Rodríguez-Galán,
J.De la cruz,
J.Bravo.
Ribosome biogenesis is one of the most essential pathways in eukaryotes although
it is still not fully characterized. Given the importance of this process in
proliferating cells, it is obvious that understanding the macromolecular details
of the interactions that take place between the assembly factors, ribosomal
proteins and nascent pre-rRNAs is essentially required for the development of
new non-genotoxic treatments for cancer. Herein, we have studied the association
between the WD40-repeat domains of Erb1 and Ytm1 proteins. These are essential
factors for the biogenesis of 60S ribosomal subunits in eukaryotes that form a
heterotrimeric complex together with the also essential Nop7 protein. We provide
the crystal structure of a dimer formed by the C-terminal part of Erb1 and Ytm1
from Chaetomium thermophilum at 2.1 Å resolution. Using a multidisciplinary
approach we show that the β-propeller domains of these proteins interact in a
novel manner that leads to a high-affinity binding. We prove that a point
mutation within the interface of the complex impairs the interaction between the
two proteins and negatively affects growth and ribosome production in yeast. Our
study suggests insights into the association of the Erb1-Ytm1 dimer with
pre-ribosomal particles.
