Structural basis of ligand-mediated transition to higher-order rubisco assemblies

Proteins often assemble as higher order complexes, underlying a diversity of molecular structures and biological functions. The emergence of protein-protein interactions between binding partners is generally considered to be the primary driver of oligomerization. However, ligand binding has also been demonstrated to affect higher-order assembly, though this phenomenon is not widely considered as a primary driver of oligomerization. Here, we describe the mechanism by which different rubisco oligomeric states are induced via ligand binding. By expanding the phylogenetic sampling of a unique clade of rubisco, we discover a range of oligomeric responses to ligand binding across the phylogeny and identify the structural features responsible for shifts in the oligomeric state that ultimately provide a path to evolving new quaternary structures. Here, we identify a ligand-dependent mechanism giving rise to new protein assemblies, in contrast with the typical process of evolving new protein-protein interfaces directly. Our findings describe a means by which binding and entrenchment of a ligand enables an increase in structural complexity.