A beta barrel is a large beta-sheet that twists and coils to form a closed structure in which the first strand is hydrogen bonded to the last. Beta-strands in beta-barrels are typically arranged in an antiparallel fashion. Barrel structures are commonly found in porins and other proteins that span cell membranes and in proteins that bind hydrophobic ligands in the barrel center, as in lipocalins. Porin-like barrel structures account for as many as 2–3% of the genes in gram-negative bacteria.
In many cases the strands contain alternating polar and hydrophobic amino acids, so that the hydrophobic residues are oriented into the interior of the barrel to form a hydrophobic core and the polar residues are oriented toward the outside of the barrel on the solvent-exposed surface. Porins and other membrane proteins containing beta barrels reverse this pattern, with hydrophobic residues oriented toward the exterior where they contact the surrounding lipids, and hydrophilic residues oriented toward the interior pore.
All beta-barrels can be classified in terms of two integer parameters: the number of strands in the beta-sheet, n, and the "shear number", S, a measure of the stagger of the strands in the beta-sheet. These two parameters (n and S) are related to the inclination angle of the beta strands relative to the axis of the barrel.
Types of beta barrels
Most beta barrels have one of three topologies:
Up-and-down beta barrel
Up-and-down barrels are the simplest barrel topology and consist of a series of beta strands, each of which is hydrogen-bonded to the strands immediately before and after it in the primary sequence.
Greek key barrels have some beta strands adjacent in space that are not adjacent in sequence. Beta barrels generally consist of at least one Greek key structural motif linked to a beta hairpin, or two successive Greek keys.
The jelly roll barrel, also known as the Swiss roll, is a complex nonlocal structure in which four pairs of antiparallel beta sheets, only one of which is adjacent in sequence, are "wrapped" in three dimensions to form a barrel shape.
Sixteen- or eighteen-stranded beta barrel structures are common in porins, which function as transporters for ions and small molecules that cannot diffuse across a cellular membrane. Such structures appear in the outer membranes of gram-negative bacteria, chloroplasts, and mitochondria. The central pore of the protein, sometimes known as the eyelet, is lined with charged residues arranged so that the positive and negative charges appear on opposite sides of the pore. A long loop between two beta sheets partially occludes the central channel; the exact size and conformation of the loop helps in discriminating between molecules passing through the transporter.
Lipocalins are typically eight-stranded beta barrel proteins that are often secreted into the extracellular environment. Their most distinctive feature is their ability to bind and transport small hydrophobic molecules. The most famous example of the family is retinol binding protein (RBP), which binds and transports retinol (vitamin A). In humans, retinol is stored in the liver and transported by RBP to other tissues. Each RBP molecule transports a single retinol molecule in a process mediated by protein-protein interactions with prealbumin and various cell-surface receptors; after the retinol has been delivered, the RBP molecule is degraded in the kidney.
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- Explanation of all-beta topologies: "orthogonal beta-sandwiches" are beta-barrels (as defined in this article); "aligned" beta-sandwiches" correspond to beta-sandwich folds in SCOP classification.
- all-beta folds in SCOP database (folds 54 to 100 are water-soluble beta-barrels).
- General classification and images of protein structures from Jane Richardson lab
- Images and examples of transmembrane beta-barrels
- Stockholm Bioinformatics Center review of transmembrane proteins
- The Lipocalin Website