Structural Determinants Of Cotranslational Protein Complex Assembly Saurav Mallik Johannes Venezian Arseniy Lobov Meta Heidenreich Hector Garciaseisdedos Todd O Yeates Ayala Shiber Emmanuel D Levy by Saurav Mallik & Johannes Venezian & Arseniy Lobov & Meta Heidenreich & Hector Garcia-seisdedos & Todd O. Yeates & Ayala Shiber & Emmanuel D. Levy instant download after payment.

SUMMARYProtein assembly into functional complexes is critical to life’s processes. While complex assembly is classically described as occurring between fully synthesized proteins, recent work showed that co-translationalassembly is prevalent in human cells. However, the biological basis for the existence of this process andthe identity of protein pairs that assemble co-translationally remain unknown. We show that co-translationalassembly is governed by structural characteristics of complexes and involves mutually stabilized subunits.Accordingly, co-translationally assembling subunits are unstable in isolation and exhibit synchronized proteostasis with their partner. By leveraging structural signatures and AlphaFold2-based predictions, we accurately predicted co-translational assembly, including pair identities, at proteome scale and across species.We validated our predictions by ribosome profiling, stoichiometry perturbations, and single-moleculeRNA-fluorescence in situ hybridization (smFISH) experiments that revealed co-localized mRNAs. Thiswork establishes a fundamental connection between protein structure and the translation process, highlighting the overarching impact of three-dimensional structure on gene expression, mRNA localization,and proteostasis.