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Beta structures An awful lot of barrels...
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Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Dec 19, 2015

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Page 1: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Beta structures

An awful lot of barrels...

Page 2: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

• Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…)

• Second biggest group of protein domain structures (after )

Page 3: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Common properties

• 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)

Page 4: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Up-and-down barrels

• Simplest topology

• Similar arrangement to TIM barrels, but without helices and all strands are antiparallel

Page 5: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Retinol-binding protein (rbp)

• Retinol binds in the inside of barrel (typical for up-and-down barrels)

Page 6: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Retinol binding site in rbp

• Hydrophobic part fits in a hydrophobic pocket

• Hydroxyl group exposed to solvent

OH

Page 7: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Alterating patterns in amino acid sequence of rbp

• Hydrophobic amino acids are facing the core• Polar, charged and a few small hydrophobic are

exposed to the solvent

Page 8: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Up-and-down barrels can contain more than 8 strands

• Porin monomer from Rhodobacter has 14 strands

Page 9: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

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

Page 10: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Neuraminidase tetramer

Page 11: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Active site in -propeller proteins

• On the top of propeller there are extensive loops

• The loops form active site

Page 12: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Greek key motifs in antiparallel barrels

Page 13: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

-crystallin

• Found in lenses of your eyes

• Each domain built from 2 greek key motifs

• One connection across the barrel between two motifs

Page 14: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

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

Page 15: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Jelly roll -barrel

Page 16: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Arrangement of strands in jelly roll barrel

Page 17: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Two Greek key motifs in jelly-roll barrel

Page 18: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

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, that is)

AH –

CHOO !

Page 19: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Comparison of all those -barrels

Up-and-down -crystallin-like

jelly-roll

Page 20: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Yet another barrel – chymotrypsin fold

• Present in chymotrypsin and all other serine proteases

• Several non-protease proteins also contain similar fold

• Six strands form the barrel

Page 21: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Structure of chymotrypsin

Domain 1

Domain 2

Page 22: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Beta helix

• Two different kinds – two-sheet helix and three-sheet helix

• Both represent deviations from idealized structure with a single spiral-like strand

Page 23: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Two sheet beta helix

Page 24: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Sequence pattern in two sheet beta helix

X7

U8

X9X7

U8

X9

• Gly-Gly-X-Gly-X-Asp-X-U-X

• X=any amino acid

• U=big hydrophobic, often Leu

• Ca ions sit in between loops

• Motif present in several bacterial proteases

Page 25: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Three sheet beta helix

Unlike two-sheet beta helices, there are no repetitive sequence patterns

Page 26: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Structure of pectate lyase

Page 27: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Spider silk

Page 28: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Structure of spider silk

• All-beta fibrous protein

• N- and C-terminal parts are variable

• A large, up to 800 residues long central region is made from repeats: -(Ala)8-10-Gly-Gly-X-

Page 29: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Structure of spider silk

Made up from beta sheets

About 30% of beta sheets form microcrystals

The rest of beta shets form a flexible matrix

Soluble form of spider silk is -helical!

Beta sheets form upon spinning

Page 30: Beta structures An awful lot of barrels.... Functionally the most diversily populated group (antibodies, enzymes, transport proteins etc…) Second biggest.

Properties of spider silk

• 5 times stronger than steel

• Very elastic – can be stretched 3-4 times its original size without breaking

• Lighter than cotton