Functionally the most diversely populated group (antibodies, enzymes, transport proteins etc…)
Second biggest group of protein domain structures (after )
Built up from four to over ten beta strands
strands are arranged in predominantly antiparallel fashion
Usually two beta sheets are formed, which pack each against other, resembling barrel or distorted barrel (=double sandwich)
Anti-parallel strands are usually arranged in two -sheets that pack against each other and form a distorted barrel structure, the core of the structure.
Depending on the way the -strands around the barrel are connected along the polypeptide chain, they can be divided into four major groups:
Greek Key barrel
Jelly roll barrel
Schematic and topological diagrams of an up-and-down barrel.
The eight strands are all antiparallel to each other and are connected by hairpin loops.
Beta strands that are adjacent in the amino acid sequence are also adjacent in the three-dimensional structure of up-and-down barrels.
Retinol-binding protein (rbp)
The structure of human plasma retinol-binding protein (RBP) is an up-and-down barrel. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule .
Retinol binding site in rbp
Hydrophobic part fits in a hydrophobic pocket
Hydroxyl group exposed to solvent
Alterating patterns in amino acid sequence of rbp
Amino acid sequence of strands 2, 3, and 4 in human plasma retinol-binding protein.
The sequences are listed in such a way that residues which point into the barrel are aligned.
These hydrophobic residues are shown by arrows and are colored green. The remaining residues are exposed to the solvent. Hydrophobic amino acids are facing the core
Polar, charged and a few small hydrophobic are exposed to the solvent
Up-and-down barrels can contain more than 8 strands
Porin monomer from Rhodobacter has 14 strands
propeller in neuraminidase
Influenza virus protein, involved in virion release from cells
Tetrameric protein, one monomer consists of 6 up-and down sheets
Builds a propeller-like structure
Active site in -propeller proteins
On the top of propeller there are extensive loops
The loops form active site
Greek Key Motifs
This motif is formed when one of the connections of four antiparallel strands is not a hairpin connection.
The motif occurs when strand number n is connected to strand n + 3 (a) or n - 3 (b) instead of n + 1 or n - 1 in an eight-stranded antiparallel sheet or barrel. The two different possible connections give two different hands of the Greek key motif.
In all protein structures known so far, only the hand shown in (a) has been observed.
The Fold of IgG Domains
Beta strands labeled A-G of the constant and variable domains of immunoglobulins have the same topology and similar structures. There are two extra strands, C' and C'' (red) in the variable domain. The loop between these strands contains the hyper-variable region CDR2. The remaining CDR regions are at the same end of the barrel in the loops connecting strands B and C and strands F and G.
Gamma Crystallin Domain
Found in lenses of your eyes
The domain structure of -crystallin is built up from two sheets of four antiparallel strands, sheet 1 from strands 1, 2, 4, and 7 and sheet 2 from strands 3, 5, 6, and 8.
It is obvious that the strands are arranged in two Greek key motifs, one (red) formed by strands 1 - 4 and the other (green) by strands 5 - 8.
Complete -crystallin Molecule
The two domains of the complete molecule have the same topology; each is composed of two Greek key motifs that are joined by a short loop region.
There is a greater amino acid sequence homology between the domains than the motifs within each domain, suggesting that the four Greek Key motifs in -crystallin are evolutionarily related by gene duplication and fusion.
Evidence for two gene duplication events in -crystallin evolution
Two domains have about 40% sequence identity
Two motifs within the domain share 20-30% sequence identity
1. 2. x 2 x 2
Jelly Roll Mo tifs
The eight strands are drawn as arrows along two edges of a strip of paper. The strands are arranged such that strand 1 is opposite strand 8, etc..
The strands follow the surface of the barrel and the loop regions provide the connections at both ends of the barrel.
Arrangement of strands in jelly roll barrel
Two Greek key motifs in jelly-roll barrel
Jelly-roll barrel in viruses
Very common in subunits of spherical viruses
Barrel is distorted and with helices instead of some loops
Example: Rhinovirus (common cold)
The Globular Head of the Hemagglutinin Subunit is a Distorted Jelly Roll Structure
strand 1 contains a long insertion, and strand 8 contains a bulge in the corresponding position. Each of these two strands is therefore subdivided into shorter strands. The loop region between strands 3 and 4 contains a short helix, which forms one side of the receptor binding site (yellow circle).
Comparison of all those -barrels Up-and-down -crystallin-like jelly-roll
Two different kinds – two-sheet helix and three-sheet helix
Both represent deviations from idealized structure with a single spiral-like strand
The two parallel sheets are colored green and red, the loop regions that connect the strands are yellow.
Each structural unit is composed of 18 residues with 9 consensus sequence Gly-Gly-X-Gly-X-Asp-X-U-X forming a -loop- -loop structure, where U is a large hydrophobic residue, often Leu.
Each loop region contains six residues of sequence Gly-Gly-X-Gly-X-Asp where X is any residue. Calcium ions are bound to both loop regions.
Extracellular bacterial proteinase
Sequence pattern in two sheet beta helix X 7 U 8 X 9 X 7 U 8 X 9
X=any amino acid
U=big hydrophobic, often Leu
Ca ions sit in between loops
Motif present in several bacterial proteases
As shown in (a), two of the sheets (blue and yellow) are parallel to each other and are perpendicular to the third (green). In (b), each structural unit is composed of three strands connected by three loop regions (labeled a, b and c).
Loop a (red) is invariably composed of only two residues, whereas the other two loop regions vary in length .
Unlike two-sheet beta helices, there are no repetitive sequence patterns