Beta structures (Antiparallel)

The 2nd large group of domain structures

 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

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

Twisted sheets form a barrel-like structure

(b) Arranged around the surface of a barrel

(c) Perpendicular to the axis

 Up and Down barrels Greek keys Jelly Roll Barrel

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

 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

8 1 2 7 4 5 6 3

Topological diagram (Eg., Hemoagglutin)

1:8, 2:7, 3:6, 4:5 Hydrogen bonded strands All adjacent strands are anti parallel

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

 Retinol binds in the inside of barrel (typical for upand-down barrels) Beta strands are curved, twisted around molecule and the wrapped retinol

C end is open to solvent,

the tail of the retinol is at the open end of the

barrel
N end is closed to tight side chain packing

Retinol binding site in rbp

Hydrophobic ligand end

fits in a hydrophobic by the pocket formed

beta strands
Hydroxyl group of retinol is exposed to solvent

 2 Sheets - 1, 2, 3, 4, 5, 6 and 1, 8, 7, 6, 5 1, 5 and 6 contribute to both having the sheets by sharp corners

where they can turn over from one sheet to the other

Amino acid sequence reflects beta structure

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

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

Porin monomer from Rhodobacter has 14 beta strands

 Influenza virus RNA Virus

Outer lipid envelope has 2 viral proteins (Hemagglutinin and Neuraminidase) that are transmembrane proteins with few

residues inside the membrane and a transmembrane region

followed by a stalk and a head piece outside the membrane Head is exposed on the surface of the virion and thus provide

antigenic determinants
Hemagglutinin is glycosylated and binds to sialic acids on glycoprotein cell receptors

Neuraminidase cleaves sialic acids thereby release newly

formed viral progeny

Neuraminidase Up and down beta sheets Homo tetrameric protein Structure first elucidated by Peter Colmans Lab, Parkville, Australia

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 barrel

with 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

 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 symmetry

around an axis through the

center of the subunit

 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

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

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

Gamma crystallin Crystallins Lens Proteins: , and crystallins crystallin Monomeric, 170 residues Structure Blundell resolved in by Tom 1.9A Each London,

resolution
Has two domains domain built from 2 greek key

motifs
One connection across the barrel between two motifs

 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

 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

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

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 roll jelly roll, there the are many such is

connections 4 connections called as jelly

because polypeptide chain wrapped around a barrel like a jelly roll

Found in coat proteins of the spherical

viruses, plant lectin concanavalin A and the hemagglutin protein

 The polypeptide chain has eight beta strands 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

 Beta strands are placed along the sides of the barrel Loop regions form the connections at the top and bottom of the barrel

 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

Comparison of all those beta-barrels

Up-and-down

g-crystallin-like

jelly-roll

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

 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

 Bacterial proteinases three times the structural unit is repeated to form a right handed coiled structure which

comprises 2 adjacent three stranded parallel beta sheets with

a hydrophobic core in between

Alpha / beta structure

Beta helix

Loop alpha helix loop connects

parallel strands Single beta sheet adjacent of a stack of alpha helices In alpha / beta structures, a twist of about 20 between adjacent beta

Loop beta strand loop

2 parallel beta sheets In beta helix structures, no such constraint is

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

present and therefore the

sheets are almost planar and form straight walls