Interaction of the periplasmic chaperone SurA with the inner membrane protein secretion (SEC) machinery

Gram-negative bacteria are surrounded by two protein-rich membranes with a peptido-glycan layer sandwiched between them. Together they form the envelope (or cell wall), crucial for energy production, lipid biosynthesis, structural integrity, and for protection against physical and chemical environmental challenges. To achieve envelope biogen-esis, periplasmic and outer-membrane proteins (OMPs) must be transported from the cytosol and through the inner-membrane, via the ubiquitous SecYEG protein-channel. Emergent proteins either fold in the periplasm or cross the peptidoglycan (PG) layer towards the outer-membrane for insertion through the 0-barrel assembly machinery (BAM). Trafficking of hydrophobic proteins through the periplasm is particularly treacher-ous given the high protein density and the absence of energy (ATP or chemiosmotic potential). Numerous molecular chaperones assist in the prevention and recovery from aggregation, and of these SurA is known to interact with BAM, facilitating delivery to the outer-membrane. However, it is unclear how proteins emerging from the Sec-machinery are received and protected from aggregation and proteolysis prior to an interaction with SurA. Through biochemical analysis and electron microscopy we demonstrate the binding capabilities of the unoccupied and substrate-engaged SurA to the inner -mem-brane translocation machinery complex of SecYEG-SecDF-YidC - aka the holo-translo-con (HTL). Supported by AlphaFold predictions, we suggest a role for periplasmic domains of SecDF in chaperone recruitment to the protein translocation exit site in SecYEG. We propose that this immediate interaction with the enlisted chaperone helps to prevent aggregation and degradation of nascent envelope proteins, facilitating their safe passage to the periplasm and outer-membrane.

Automated summary

Gram-negative bacteria have a protein-rich envelope crucial for various functions like energy production and protection against environmental challenges. Proteins are transported through the envelope by molecular chaperones like SurA. The interaction between SurA and the Sec-machinery helps prevent protein aggregation and degradation, ensuring safe passage of proteins to the periplasm and outer-membrane.