Protein%20Secondary%20Structure

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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 neutralized
through hydrogen bonds ?Solution Regular
secondary structure
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a Helix

• Discovered 1951 by Pauling
• 5-40 aa long
• Average 10aa
• Right handed
• Oi-NHi4 bb
• atoms satisfied
• p helix i - i5
• 310 helix i - i3

1.5?/res
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a Helix is a Dipole
and binds negative charges at N-term
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Side Chains project out from the Helix
View down one helical turn
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Proline Disrupts Helix
No donor!
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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 Block the continuation of
the helix by hydrogen bonding with the
donor (NH) of N3
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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
?
F
w
The peptide bond w is planar and polar
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Ramachandran Plots
?
F
Glycine flexible backbone
All except Glycine
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Ramachandran Plots
?
F

• 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
Closed barrel
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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
G
G
S,T
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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
• Transmembrane proteins
• Structural and motile proteins
• Fibrous proteins (Keratin)
• Fibrinogen, myosin
• Coiled-coils (Leucine Zippers)
• 4-helix-bundles
• a-helical domains
• Globins

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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-i4 ridge
• Globins
• i-i3 ridge
• ROP

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ALPHA a-Helical Domains

• gt20 a helices form globular domain
• Example muramidase
• 27 helices
• right-handed
• superhelical twist
• Hole in center

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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
• Usually enzymes

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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
• Polar aas (KRE) at tip of barrel participate in
  formation of hydrophobic core

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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)
• Many different arrangements

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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 Barrel composed of
anti-parallel strands with hairpin
connections Propeller multi-domain protein
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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, etc

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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 MotifWrapped around a Barrel
Composed of repeats of greek keys Concavalin,
Hemagglutinin
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BETA b-helix Structures
Right-handed coiled structure 18aa 6 in loop 3
in b GGXGXDXUX (Uhydrophobic) Loop
stabilized by Ca ion Pectate lyase
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Additional Useful Material
http//swissmodel.expasy.org/course/text/