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Protein Secondary
Structure
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1958: Kendrew Solves the
Structure of Myoglobin
“Perhaps the most remarkable features of
the molecule are its complexity and its
lack of symmetry. The arrangement
seems to be almost totally lacking in the
kind of regularities which one instinctively
anticipates, and is more complicated
than has been predicted by any theory of
protein structure”
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Protein Secondary Structure
Protein interior: Hydrophobic core
Main chain folds also into interior, but it
is highly polar
→Problem: Polar atoms must be
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neutralized through hydrogen bonds
→Solution: Regular secondary
structure
a Helix
• Discovered 1951 by Pauling
• 5-40 aa long
• Average: 10aa
• Right handed
• Oi-NHi+4 : bb
atoms satisfied
• p helix: i - i+5
• 310 helix: i - i+3
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1.5Ǻ/res
a Helix is a Dipole
… and binds negative charges at N-term
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Side Chains project out from the Helix
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View down one helical turn
Proline Disrupts Helix
No donor!
CO
N
C
H2C
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CH2
CH2
H
Frequent Amino Acids at the
N-terminus of a helices
Ncap, N1, N2, N3 …….Ccap
Pro
Blocks the continuation of the helix by its
side chain
Asn, Ser
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Block the continuation of the helix by
hydrogen bonding with the donor (NH)
of N3
Helices of Different Character
Buried, partially exposed, and exposed
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Representation: Helical Wheel
Buried,
partially exposed,
and exposed
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Dihedral Angles F and 
define Backbone Geometry

w
F
The peptide bond w is planar and polar
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Ramachandran Plots

F
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All except
Glycine
Glycine: flexible
backbone
Ramachandran Plots

F
a helix: F,  around -60,-50, respectively
Other defined regions: b strand and loops
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b-Sheet
• Involves several regions in sequence
• Oi-NHj
•Parallel and
anti-parallel
sheets
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Antiparallel b-Sheet
• Parallel Hbonds
• Residue side chains point up/down/up ..
• Pleated
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Parallel b-Sheet
• Less stable than antiparallel sheet
• Angled
hbonds
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Combined b-Sheet
Rare: strains in middle strand
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Examples of b-Sheet Topologies
Topology
diagram
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Closed barrel
Connecting Elements of
Secondary Structure defines
Tertiary Structure
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Loops
• Connect helices and strands
• At surface of molecule
• More flexible
• Contain functional sites
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Hairpin Loops (b turns)
• Connect strands in antiparallel sheet
G,N,D
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G
G
S,T
Super Secondary Structures:
(1) Greek Key Motif
• 24 possible topologies for 2 hairpins
• 8 found
• Most common: Greek key motif
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Super Secondary Structures:
(2) b-a-b Motif
• Connect strands in parallel sheet
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Repeated b-a-b Motif Creates
b-meander: TIM Barrel
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Large Polypeptide Chains Fold into
Several Domains
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Protein
Classification
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Protein Classification
Alpha
contain only a helices
Beta
contain only b sheets
Alpha/Beta
contain combination of both
Alpha + Beta contain domains of a and b
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ALPHA
Occur in
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• Transmembrane proteins
• Structural and motile proteins
• Fibrous proteins (Keratin)
• Fibrinogen, myosin
• Coiled-coils (Leucine Zippers)
• 4-helix-bundles
• a-helical domains
• Globins
ALPHA: Coiled-Coils
Francis Crick, 1953: maximal sc interactions
if two helices are wound around each other
• Left-handed supercoil: 3.5 residues/turn:
Heptad repeat
• “knobs-into-holes”
• Leucine zipper motif in Transcription Factors
(more about this later..)
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ALPHA: 4-Helix Bundle
• “ridges-into-grooves”
ROP
protein
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Ridges-into-Grooves
2 possible
arrangements:
• i-i+4 ridge:
Globins
• i-i+3 ridge:
ROP
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ALPHA: a-Helical Domains
>20 a helices form globular domain
Example: muramidase
• 27 helices
• right-handed
superhelical twist
•Hole in center
ALPHA/BETA
Most frequent
3 classes:
• Barrel
• Twisted sheet
• Horseshoe fold
• Functional sites in loop regions
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ALPHA/BETA: Barrels
• Consecutive a-b-a units
in same orientation
• Usually 8; b8-hb- b1
→ closed core of b strands
•TIM barrel
Triose Phosphate Isomerase
• 34Usually enzymes
TIM Barrels
aa2,4 point out to helices
• branched aas V,I,L
aa1, 3, 5 point into barrel
• Bulky hydrophobic aas form
tightly packed hydrophobic
core
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Polar aas (KRE) at tip of
barrel: participate in formation
of hydrophobic core
TIM Barrels
Active site formed by loops at
one end of the barrel
Distinct from structural region
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ALPHA/BETA: Open Sheet
• Consecutive a-b-a units
in opposite orientation:
helices on both sides
• Rossman Fold
(discovered in 1970 in lactate
dehydrogenase)
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• Many different
arrangements
Open Sheet: Functional Sites at
Topological Switch Points
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ALPHA/BETA: Horseshoe Fold
• Consecutive a-b-a units in same orientation
• Not closed: horseshoe
•Ribonuclease
Inhibitor
• One side points to helix,
• The other is exposed
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Horseshoe Fold
Leucine-rich repeats
• each ~30aa
• L responsible for packing
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BETA
Antiparallel b structures
Usually two sheets packed
against each other
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Barrel: composed of
anti-parallel strands
with hairpin connections
Propeller: multi-domain
protein
BETA Barrels
Retinol-binding protein
8 strands
Center:
hydrophobic pocket
binds lipids
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BETA Propellors (I)
Neuraminidase
• 6 b-sheets (each 4
strands) organized as
propellor blades
• Active site formed by
loops from each blade
Others: G-proteins,
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etc
BETA Propellors (II)
Neuraminidase
• 6 b-sheets (each 4
strands) organized as
propellor blades
• Active site formed by
loops from each blade
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BETA Propellors (III)
Neuraminidase
• 6 b-sheets (each 4
strands) organized as
propellor blades
• Active site formed
by loops from each
blade
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BETA: Jelly-Roll Motif
Wrapped around a Barrel
Composed of repeats
of greek keys
Concavalin,
46 Hemagglutinin
BETA: b-helix Structures
Right-handed coiled structure
18aa: 6 in loop + 3 in b
GGXGXDXUX (U=hydrophobic)
Loop stabilized by Ca ion
Pectate lyase
Additional Useful Material
http://swissmodel.expasy.org/course/text/
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