Beta barrel

A canonical beta-barrel protein, a sucrose-specific porin from the bacterium Salmonella typhimurium, viewed from the side. Porins are transmembrane proteins with hollow centers through which small molecules can diffuse.

File:Rbp 1brp.png

The human retinol-binding protein (RBP), a canonical lipocalin eight-strand barrel binding retinol (vitamin A).

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 are encoded by 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.

Jelly roll

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.

Some functions of beta barrels

Porins

Main article: Porin (protein)

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.

Preprotein translocases

Beta barrels also function within endosymbiont derived organelles such as mitochondria and chloroplasts to transport proteins. Within the mitochondrion two complexes exist with beta barrels serving as the pore forming subunit, Tom40 of the Translocase of the outer membrane, and Sam50 of the Sorting and assembly machinery. The chloroplast also has functionally similar beta barrel containing complexes, the best characterised of which is Toc75 of the TOC complex (Translocon at the outer envelope membrane of chloroplasts).

Lipocalins

File:MupwithSBT.jpg

A mouse major urinary protein bound to 2-sec-butyl-4,5-dihydrothiazole (SBT), a mouse pheromone. The beta barrel forms a calyx, in which the SBT molecule is tightly bound.

Main article: Lipocalin

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 in a beta barrel calyx. Examples of the family include retinol binding proteins (RBPs) and major urinary proteins (Mups). RBP binds and transports retinol (vitamin A), while Mups bind a number of small, organic pheromones, including 2-sec-butyl-4,5-dihydrothiazole (abbreviated as SBT or DHT), 6-hydroxy-6-methyl-3-heptanone (HMH) and 2,3 dihydro-exo-brevicomin (DHB).

Shear number

A piece of paper can be formed into a cylinder by bringing opposite sides together. The two edges come together to form a line. Shear can be created by sliding the two edges parallel to that line. Likewise, a beta barrel can be formed by bringing the edges of a beta sheet together to form a cylinder. If those edges are displaced, then shear will be created.

A similar definition of shear is found in geology, where shear refers to a displacement within rock perpendicular to the surface of the rock. In physics, the amount of displacement is referred to as shear strain, which has units of length. Shear number is a measure of shear strain in which the displacement is measured in units of "amino acid residues".

The determination of shear number requires the assumption that each amino acid in one strand of a beta sheet is adjacent to just one amino acid in the neighboring strand. (This assumption may not hold if, for example, a beta bulge is present. ) To illustrate, S will be calculated for green fluorescent protein. This protein was chosen because the beta barrel contains both parallel and antiparallel strands. The particular example used, PDB: 1RRX​, is one of the few structures of this protein that is not obtained from a mutant protein.

• Green fluorescent protein 1RRX
• 1RRX pdb structures.png

  Eleven strands make up the beta barrel.

• 1RRX pdb group.png

  The chain is colored according to position in the chain, from blue (the N terminus) to red (the C terminus).

From the last figure, the order of strands in the barrel is found to be: 1 6 5 4 9 8 7 10 11 3 2.

To determine which amino acid residues are adjacent in the beta strands, the location of hydrogen bonds is determined. The figure below shows the calculated positions of hydrogen bonds. The residues are labeled with a residue number and a one-letter amino acid code (the label is placed near the alpha carbon). Only the backbone atoms of the beta barrel are shown, and, of that, only the front slab is shown. It appears that, for example, residues 31 G, on strand 2, 16 V on strand 1, and 121 N on strand 6 are adjacent.

File:1RRX pdb slab 1.png

The first of four slabs showing hydrogen bonding between strands.

• The other three slabs
• 1RRX pdb slab 2.png

  Slab 2, obtained by rotating the protein by 90°.

• 1RRX pdb slab 3.png

  Slab 3, obtained by rotating an additional 90°.

• 1RRX pdb slab 4.png

  Slab 4, obtained by rotating an additional 90°.

The data from the figures is collected in the table, below. Each column contains the residues in one strand. Strand 1 is repeated in the last column. The arrows indicate the hydrogen bonds that were identified in the figures. The relative direction of each strand is indicated by the "+" and "-" at the bottom of the table. Except for strands 1 and 6, all strands are antiparallel. The parallel interaction between strands 1 and 6 accounts for the different appearance of the hydrogen bonding pattern. (Some arrows are missing because not all of the hydrogen bonds expected were identified. Also, some residues, such as 182 ?, contain a question mark; this indicates the presence of a non-standard amino acid.) The side chains that point to the outside of the barrel are in bold.

File:Shear Number GFP.svg

Table for calculating the shear number

If no shear were present in this barrel, then residue 12 V, say, in strand 1 should end up in the last strand at the same level as it started at. However, because of shear, 12 V is not at the same level: it is 14 residues higher than it started at, so its shear number, S, is 14.

Dynamical features

Beta-barrels in proteins may carry out low-frequency breathing-like motion as observed by the Raman spectroscopy and analyzed with the quasi-continuum model. For more about the low-frequency collective motions in biomacromolecules and its biological function, see low-frequency collective motion in proteins and DNA.

References

Further reading

• Branden C, Tooze J. (1999). Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY. ISBN 0-8153-2304-2.

External links

• 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