10. Beta Domain Structure

7/27/2019 10. Beta Domain Structure

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Beta structures (Antiparallel)

The 2nd large group of domain structures


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Functionally the most diverse populated group (antibodies,

enzymes, transport proteins, cell surface proteins, coat

proteins etc)

Second biggest group of protein domain structures (after

a/b)

Built up from 4 to 5, over ten beta strands

Beta strands are arranged in predominantly antiparallel

fashion

Usually two beta sheets are formed, twisted and when

packed against other, resemble barrel or distorted barrel

The core of the barrel is formed by beta strands and the

surface is formed by residues from the loops and the beta

strands


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Twisted sheets form a barrel-like structure

Superoxide Dismutase breaks

superoxide radicals into H2O2 and

O2

Beta structure 8 Antiparallel

beta strands 2 sheets

2 metal atoms Cu and Zn


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Twisted sheets form a barrel-like structure

(b) Arranged around the surface

of a barrel

(c) Perpendicular to the axis


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Up and Down barrels

Greek keys

Jelly Roll Barrel


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Up-and-down barrels

Simplest topology

Obtained if each successive beta

strand is added adjacent to the

previous strand until the last strand

is joined by H-bond to the 1st strand

and the barrel is closed


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Eight beta strands are anti

parallel to each other

Connections are by hairpin

loops

Similar arrangement to TIM

barrels, but without helices

strands

4 times it crosses up and

down the barrel


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Topological diagram (Eg., Hemoagglutin)

1:8, 2:7, 3:6, 4:5 Hydrogen bonded strands

All adjacent strands are anti parallel

8 1 2 7 4 5 6 3


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Retinol-binding protein (rbp)

Transport protein for retinol

Monomeric protein with 180 residues

Single binding site for the hydrophobic ligand retinol

Beta barrel core consisting of eight up and down antiparallel

strands


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Retinol binding site in rbp

Hydrophobic ligand end

fits in a hydrophobic

pocket formed by the

beta strands

Hydroxyl group of retinol

is exposed to solvent


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2 Sheets - 1, 2, 3, 4, 5, 6

and 1, 8, 7, 6, 5

1, 5 and 6 contribute to

both the sheets by

having sharp corners

where they can turn over

from one sheet to the

other


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In most of the surface of RBP, side chains from residues with

beta strands are exposed to the solvent Acheived by alternating hydrophobic residues with polar or

charged hydrophilic residues in the amino acids of beta strands Side chains of the beta strands form the hydrophobic core of the

barrel as well as part of the hydrophilic outer surface

Amino acid sequence reflects beta structure


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

Porin monomer from Rhodobacter has 14 beta strands


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Neuraminidase Up and down beta sheets

Homo tetrameric protein

Structure first elucidated by Peter Colmans Lab, Parkville,

Australia


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Neuraminidase tetramer - 6 bladed propeller

The whole molecule is around 1600 residues composed of 4

identical polypeptide, each of which is folded into a super barrelwith 24 beta strands

These 24 beta strands are arranged in six similar motifs each of

which contains 4 beta strands that form the six blades of a propeller

like structure


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Motif consists of up and down

anti parallel beta sheets of 4

strands The sheets exhibit larger

twists in such a way that the

direction of the 1st and 4th

strand differ by 90

The six motifs are arranged

within each subunit with an

approximate sixfold symmetryaround an axis through the

center of the subunit


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The topology diagram is identical within six beta sheets in

each subunit Most of the connections are on top, 4th strand is connected

across the top of the subunit to the 1st strand of the next

sheet

The loop that connects strands 2 and 3 is also at the top of

the subunit

Overall 12 loops are present on the top and also on the

same side

Th ti it i i th iddl f id f th ll


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The active site is in the middle of one side of the propeller

The beta sheets are arranged cyclically around an axis

through the center of the molecule

The loop regions at the top of the barrel are extensive and

together they form a wide funnel shaped pocket containing

the active site


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Greek key motifs in antiparallel b barrels

Greek key motifs occurs in anti parallel structures

Motif is formed when strand no n is connected to an anti

parallel strand at the same end of the barrel and the

connection is n+3 or n-3 instead of n+1 or n-1

If it is n+1 or n-1, it results in up and down barrel structures

The remaining strands are connected by up and down

connections or by another Greek key motif


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Gamma crystallin

Crystallins Lens Proteins: ,

and crystallins crystallin Monomeric, 170

residues

Structure resolved by Tom

Blundell in London, 1.9A

resolution

Has two domains Each

domain built from 2 greek key

motifs

One connection across the

barrel between two motifs


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Schematic diagram of the path of the polypeptide chain in one

domain of the gamma crystallin molecule. The domain

structure is built up from two beta sheets of four antiparallel

beta strands


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Sheet 1 from beta strands 1, 2,

4, 7 and sheet 2 from strands

3, 5, 6, 8. The strand order is 2,

1, 4, 7 and 6, 5, 8, 3

7 and 6 are adjacent although

not hydrogen bonded to each

other on the back side of the

domain

Space between 7 and 6

indicate that they belong to

different sheets


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The two domains have identical topology

2 domains have same topology, each is composed of 2 greek

key motifs that are joined by a short loop region

Topologically the polypeptide chain is divided into 4

consecutive greek key motifs arranged in 2 domains


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Jelly roll beta barrel

Variation of greek key motif

In greek key motif, one of the connections

is made across one end of the barrel

In jelly roll, there are many such

connections 4 connections called as jelly

roll because the polypeptide chain is

wrapped around a barrel like a jelly roll

Found in coat proteins of the spherical

viruses, plant lectin concanavalin A and the

hemagglutin protein


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The polypeptide chain has eight betastrands interrupted by loop regions

The beta strands are arranged in a

long antiparallel hairpin such that

strand 1 is hydrogen bonded to

strand 8, strand 2 to 7 and so on


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Beta strands are placed along the

sides of the barrel

Loop regions form the connections

at the top and bottom of the barrel


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The hydrogen bonded anti parallel beta strand pairs 1:8, 2:7,

3:6 and 4:5 are now arranged such that beta strand 1 is

adjacent to strand 2, 7 is adjacent to 4, 5 to 6 and 3 to 8

All adjacent beta strands are antiparallel


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Comparison of all those beta-barrels

Up-and-down g-crystallin-like jelly-roll


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Parallel Beta Helix domains have a novel

fold

Beta helix (1993)

Found in bacterial pectate lyase,

bacterial proteinases, bacteriophage P22

tailspike protein

The polypeptide chain is coiled into a

wide helix, formed by beta strands

separated by loop regions


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Simplest form 2 sheet beta helix where each

turn of the helix comprises two beta strands

and two loop regions 18 amino acids, 3 in each strand and 6 in each

loop

Specific amino acid pattern double repeat of a

nine residue consensus sequence of Gly-Gly-X-

Gly-X-Asp-X-U-X

X is any amino acid and U is large, hydrophobic

residue usually Leucine

Gly-Gly-X-Gly-X-Asp forms the loop structure

X-U-X forms the beta strand

The loops are stabilized by the Ca ions which

bind to the Asp residues


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Bacterial proteinases three times the structural unit is

repeated to form a right handed coiled structure whichcomprises 2 adjacent three stranded parallel beta sheets with

a hydrophobic core in between


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Alpha / beta structure Beta helix

Loop alpha helix loop connects

parallel strands

Loop beta strand loop

Single beta sheet adjacent of a stack

of alpha helices

2 parallel beta sheets

In alpha / beta structures, a twist of

about 20 between adjacent beta

strands is imposed by the packing

requirements of the alpha helices in

order to pack ridges into grooves.

Hence the alpha helices has to be

twisted with respect to each other

and this forces the beta strands also

to be twisted

In beta helix structures,

no such constraint is

present and therefore the

sheets are almost planar

and form straight walls

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10. Beta Domain Structure