Transcript Beta Structures

Beta Structures
• Anti-parallel b strands are usually
arranged in two b-sheets that
pack against each other and form
a distorted barrel structure, the
core of the structure.
• Depending on the way the bstrands around the barrel are
connected along the polypeptide
chain, they can be divided into
four major groups:
Up-and-down barrel
superoxide dismutase (SOD)
Greek Key barrel
Jelly roll barrel
b-helix
Up-and-down
Barrel
• The eight b 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 threedimensional structure of
up-and-down barrels.
Green Fluorescent Protein
 from Aequorea victoria (jellyfish)
 11-stranded b-barrel with central -helix
 chromophore formed during folding
(from residues S65, Y66, G67) is
contained in the middle of the barrel
 contains 1 Trp, 10 Tyr
 Many current uses as reporters of gene
expression and biosensors.
Excitation 395 nm and 475 nm
Emission 506 nm
http://www.plantsci.cam.ac.uk/Haseloff/GFP/GFPbackgrnd.html
Retinol-binding Protein (RBP)
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The structure of human plasma retinol-binding protein (RBP) is an upand-down b barrel.
Plasma RBP is a temporary protein that binds and transports a retinol
molecule (vitamin A) from the liver to dependent tissues
Retinol is bound inside the barrel, between the two b sheets, such that
its only hydrophilic part (an OH tail) is at the surface of the molecule.
Exhibits only minimal conformational changes in both apo- (open) and
holo- (bound) forms.
Amino Acid Sequence Reflects b
Structure
• Amino acid sequence of b 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 form the barrel core,
while the remaining residues are exposed to the
solvent.
Beta Structures
Greek Key Motifs•
This motif is formed when one
of the connections of four
antiparallel b 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 b 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
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IgG (immunoglobulin) domains, found in antibodies, incorporate Greek Key
motifs.
Beta strands labeled A-G of the constant and variable domains of
immunoglobulins have the same topology and similar structures. There are
two extra b strands, C' and C'' (red) in the variable domain. The loop between
these strands contains the hyper-variable region CDR2, which is modified for
antigen specificity. The remaining CDR regions are at the same end of the
barrel in the loops connecting b strands B and C and strands F and G.
Gamma Crystallin Domain
• The domain structure of g-crystallin is built up from two b sheets
of four antiparallel b strands, sheet 1 from b strands 1, 2, 4, and
7, and sheet 2 from strands 3, 5, 6, and 8.
• The b strands are arranged in two Greek key motifs, one (red)
formed by strands 1 - 4 and the other (green) by strands 5 - 8.
Complete g-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 identity
between the domains than
the motifs within each
domain, suggesting that the
four Greek Key motifs in gcrystallin are evolutionarily
related by gene duplication
and fusion.
Jelly Roll Motifs
• The eight b 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..
• These are archael
proviruses from the
PRD1-Adenovirus
lineage.
• Usually arranged in 2
sheets.
• Can be more than 8
strands, as long as even
number.
Two-sheet b helix.
• Antiparallel sheets.
• Each structural unit is composed
of 18 residues with a 9 residue
consensus sequence Gly-Gly-XGly-X-Asp-X-U-X forming a bloop-b-loop structure, where U is
a large hydrophobic residue,
often Leu.
• Each loop region contains six
residues of sequence Gly-Gly-XGly-X-Asp where X is any
residue.
• Calcium ions are bound to both
loop regions by D residues.
• G residues provide loop flexibility.
X
X
U
U
X
X
Extracellular bacterial proteinase
Three-sheet b Helix
• As shown in (a), two of the b 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 b
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.
Beta Structures
Visualization using Chimera
PDBfile 2kfb
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“Structure of the cataract causing P23T mutant of human gamma-D
Crystallin.” Jung, J. (2009) Biochemistry 48: 2597-2609.
PDBfile 4jgf, 1h4a.
PDB
Species
WT / mutant Method
1h4a
Human
WT
Xray 1.15A
2kfb
Human
P23T
NMR
4jgf
Human
P23T
Xray
2.5 A