protein secondary structure 1. 1958: kendrew solves the structure of myoglobin “perhaps the most...
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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 coreMain chain folds also into interior, but it
is highly polar
→Problem: Polar atoms must be neutralized through hydrogen bonds
→Solution: Regular secondary structure3
Helix• Discovered 1951 by Pauling• 5-40 aa long• Average: 10aa• Right handed • Oi-NHi+4 : bb atoms satisfied
• helix: i - i+5
• 310 helix: i - i+3 1.5Ǻ/res
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Helix is a Dipole
… and binds negative charges at N-term5
Side Chains project out from the Helix
View down one helical turn6
Proline Disrupts Helix
No donor!
N
CO
C H
CH2
CH2H2C
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Frequent Amino Acids at the N-terminus of helices
Pro Blocks the continuation of the helix by its side chain
Asn, SerBlock the continuation of the helix by
hydrogen bonding with the donor (NH) of N3
Ncap, N1, N2, N3 …….Ccap
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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 and define Backbone Geometry
The peptide bond is planar and polar11
Ramachandran Plots
Glycine: flexible backbone
All except Glycine
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Ramachandran Plots
helix: around -60,-50, respectivelyOther defined regions: strand and loops
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Sheet
• Involves several regions in sequence• Oi-NHj
•Parallel andanti-parallelsheets
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Antiparallel Sheet
• Parallel Hbonds• Residue side chains point up/down/up ..• Pleated
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Parallel Sheet
• Less stable than antiparallel sheet• Angled hbonds
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Combined Sheet
Rare: strains in middle strand
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Examples of Sheet Topologies
Topology diagram
Closed barrel18
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 ( 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) Motif
• Connect strands in parallel sheet
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Repeated Motif Creates -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 helices
Beta contain only sheets
Alpha/Beta contain combination of both
Alpha + Beta contain domains of and
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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• -helical domains• Globins28
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-Grooves2 possible arrangements:
• i-i+4 ridge:Globins
• i-i+3 ridge:ROP
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ALPHA:-Helical Domains
>20 helices form globular domainExample: muramidase
• 27 helices• right-handed superhelical twist•Hole in center
ALPHA/BETA
Most frequent3 classes:• Barrel• Twisted sheet• Horseshoe fold
• Functional sites in loop regions
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ALPHA/BETA: Barrels
• Consecutive units in same orientation
• Usually 8; 8-hb- 1
→ closed core of strands
•TIM barrelTriose Phosphate Isomerase
• Usually enzymes34
TIM Barrelsaa2,4 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 core35
TIM Barrels
Active site formed by loops at one end of the barrel
Distinct from structural region36
ALPHA/BETA: Open Sheet
• Consecutive units in opposite orientation: helices on both sides
• Rossman Fold (discovered in 1970 in lactate dehydrogenase)
• Many different arrangements37
Open Sheet: Functional Sites at Topological Switch Points
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ALPHA/BETA: Horseshoe Fold
• Consecutive 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 structures
Usually two sheets packedagainst each other
Barrel: composed of anti-parallel strands with hairpin connectionsPropeller: multi-domain protein41
BETA Barrels
Retinol-binding protein
8 strands
Center: hydrophobic pocketbinds lipids
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BETA Propellors (I)
Neuraminidase
• 6 -sheets (each 4 strands) organized as propellor blades• Active site formed by loops from each blade
Others: G-proteins, etc43
BETA Propellors (II)
Neuraminidase
• 6 -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 -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, Hemagglutinin46
BETA: -helix Structures
Right-handed coiled structure18aa: 6 in loop + 3 in GGXGXDXUX (U=hydrophobic)Loop stabilized by Ca ionPectate lyase
Additional Useful Material
http://swissmodel.expasy.org/course/text/
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