Diverging co-translational protein complex assembly pathways are governed by interface energy distribution.

Protein-protein interactions are at the heart of all cellular processes, with the ribosome emerging as a platform, orchestrating the nascent-chain interplay dynamics. Here, to study the characteristics governing co-translational protein folding and complex assembly, we combine selective ribosome profiling, imaging, and N-terminomics with all-atoms molecular dynamics. Focusing on conserved N-terminal acetyltransferases (NATs), we uncover diverging co-translational assembly pathways, where highly homologous subunits serve opposite functions.

Purification of Ribosome-Nascent-Chain Complex for Ribosome Profiling and Selective Ribosome Profiling.

Selective Ribosome Profiling (SeRP) is an emerging methodology, developed to capture cotranslational interactions in vivo. To date, SeRP is the only method that can directly capture, in near-codon resolution, ribosomes in action. Thus, SeRP allows us to study the mechanisms of protein synthesis and the network of protein-protein interactions that are formed already during synthesis.

A Global Analysis of Kinase Function in Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1.

The human pathogenic fungus can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter.

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis.

Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections.