Biogenesis of beta-barrel membrane proteins in bacteria and eukaryotes: evolutionary conservation and divergence

Abstract

Membrane-embedded beta-barrel proteins span the membrane via multiple amphipathic beta-strands arranged in a cylindrical shape. These proteins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. This situation is thought to reflect the evolutionary origin of mitochondria and chloroplasts from Gram-negative bacterial endosymbionts. beta-barrel proteins fulfil a variety of functions; among them are pore-forming proteins that allow the flux of metabolites across the membrane by passive diffusion, active transporters of siderophores, enzymes, structural proteins, and proteins that mediate protein translocation across or insertion into membranes. The biogenesis process of these proteins combines evolutionary conservation of the central elements with some noticeable differences in signals and machineries. This review summarizes our current knowledge of the functions and biogenesis of this special family of proteins.

Fig. 1

Crystal structure of a bacterial β-barrel outer membrane protein. Left: a ribbon representation of the structure of LpxR, a lipid A deacylase of Salmonella typhimurium [133]. The 12-stranded β-barrel consists of all anti-parallel β-strands, which are connected by short turns at the periplasmic side (bottom) and longer loops including some α-helical segments at the extracellular side (top). The ribbon is colored with a gradient from the N terminus in blue to the C terminus in red. Right a top view of the protein (the figure was kindly provided by Lucy Rutten)

Fig. 2

Biogenesis of bacterial outer membrane proteins. OMPs are synthesized in the cytoplasm as precursors with an N-terminal signal sequence (SP) (1). Next, they are transported across the inner membrane (IM) to the periplasm via the Sec translocon (2). The holding chaperones SecB and Skp prevent premature folding and aggregation of the OMPs in the cytoplasm and periplasm, respectively. The OMPs are then targeted to the Bam complex in the outer membrane (OM) (3), which consists of the integral membrane protein Omp85 (BamA) and four membrane-associated lipoproteins BamB–E (alternative names indicated on figure in parentheses). Omp85 consists of a C-terminal β-barrel embedded in the membrane and an N-terminal part consisting of five polypeptide-transport-associated (POTRA) domains (P1–P5) extending in the periplasm. The periplasmic chaperone SurA assists in the folding of the OMPs at the Bam complex that assembles them into the outer membrane, where they can reside as monomers or oligomers

Fig. 3

Working model for the biogenesis of mitochondrial β-barrel proteins. Precursors are synthesized in the cytosol and are probably guided to the mitochondrial surface by chaperones (1). At the mitochondrial surface, precursors are engaged by the primary import receptors of the TOM complex, predominantly via an interaction with Tom20. Subsequently, they are translocated through the TOM pore across the mitochondrial outer membrane (OM) into the intermembrane space (IMS) (2), where they interact with the small Tim protein complexes, which exert a chaperone-like function (3). Through a second step of recognition, the precursor proteins are sorted to the TOB complex, which then promotes their integration into the lipid core of the outer membrane (4)