8. Günter Kramer / Bernd Bukau - Coordination of translation and assembly of protein complexes

A large percent of any proteome of living cells acquires function only when participating in oligomeric protein complexes, but little is known about the process of protein complex assembly. In the previous funding period, we established that in five of the six bacterial protein complexes examined, complex assembly begins co-translationally involving subunit association with nascent chains of partner subunits once the contact interphase is exposed on the surface of the translating ribosome. We will use a set of suitable protein complexes, and focus on mechanistic aspects of protein complex assembly in E. coli and how the assembly mechanism integrates with the actively translating ribosome. Specifically, we will first investigate nascent chain interactions per se. Using ribosome profiling, biochemical and genetic methodologies, we will investigate structural and kinetic features of nascent chain interactions. We will then also investigate how organization of genes in operons affects co-translational assembly and determine the effect of translation speed on subunit assembly. This will elucidate the interplay between physical and genetic information decoded and transmitted during translation into 3-dimensional protein complex assembly, and cellular function.