Membrane proteins comprise ~35% of proteome and confer essential functions to biological membranes. However, the biogenesis of membrane proteins also poses enormous challenges to cellular protein homeostasis during their biogenesis. By studying the biogenesis of Light Harvesting Complex (LHC) in photosynthetic organisms, we discovered a novel dual functional chaperone, cpSRP43, which protects and guides the membrane targeting of LHC proteins. In addition, cpSRP43 also serves as a thermo-protectant for plants under heat stress by protecting chlorophyll biosynthesis enzymes from heat denaturation. As an added bonus, cpSRP43 also harbors a novel ‘disaggregase’ activity that is driven by ATP-independent binding interactions with its client proteins. Exploiting this system provides a unique opportunity to understand the mechanism and regulation of ATP-independent chaperones dedicated to membrane proteins. The simplicity and robustness of cpSRP43 also makes it an excellent candidate for protein engineering to generate improved chaperones for intervention in protein aggregation problems.

Dual role of cpSRP43 in light harvesting complex (LHC) assembly.cpSRP43 harbors two distinct chaperone activities: as a dedicated chaperone to mediate the protection and delivery of LHCPs (left), and as a general chaperone for the thermoprotection of TBS enzymes (right). Under normal conditions (left), cpSRP54 binds and optimizes the conformation of cpSRP43 for interaction with and protection of LHCP, while also inhibiting the chaperone activity of cpSRP43 towards TBS enzymes. At the thylakoid membrane, cpSRP54 docks with cpFtsY, and Alb3’s stromal domain interacts with cpSRP43 to trigger the release of LHCP and mediate insertion into the thylakoid membrane. At elevated temperatures (right), the interaction of cpSRP54 for cpSRP43 is weakened, increasing the available pool of apo-cpSRP43 that can effectively protect TBS enzymes from heat-induced aggregation.