1 research outputs found
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
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 fromChaetomium
thermophilum at 2.1 ˚
A resolution. Using a multidisciplinary approach we show that the -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
particle