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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