Proteins
Proteins?
What is its
What is its
How does it
How does it
How is its
How does it
How is it
Where is it
What are its
R2
H
O
H2N
C
N
H
R1
O
H
H
O
H
C
C
C
OH
H
O
R2
H
H
O
H2N
H
C
R1
C
N
C
OH
C
H
O
Condensation reaction forms a
peptide bond.
a
a
Peptide bond formation
The peptide bond
Peptide
The planar peptide bond
Three bonds separate sequential a carbons in a polypeptide chain. The N—Ca and Ca—C bonds can rotate, described by dihedral angles
designated f and y, respectively. The C—N peptide bond is not free to rotate.
• Rotation around the peptide bond is not permitted
• Rotation around bonds connected to the alpha carbon is permitted
• f (phi): angle around the a-carbon—amide nitrogen bond
• y (psi): angle around the a-carbon—carbonyl carbon bond
• In a fully extended polypeptide, both f and y are 180°
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Steric Hindrance
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While many angles of rotation are possible, only a few
are energetically favorable
Ramchandran plot
• Some f and y combinations are very unfavorable because of steric crowding of
backbone atoms with other atoms in the backbone or side-chains
• Some f and y combinations are more favorable because of chance to form
favorable H-bonding interactions along the backbone
• Ramachandran plot shows the distribution of f and y dihedral angles that
are found in a protein
• shows the common secondary structure elements
• reveals regions with unusual backbone structure
While many angles of rotation are
possible only a few are energetically
favorable
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Rotation
Alpha helix
• The backbone is more compact with the y dihedral (N–Ca—C–N) in the
range ( 0° <y < -70°)
• Helical backbone is held together by hydrogen bonds between the nearby
backbone amides
• Right-handed helix with 3.6 residues (5.4 Å) per turn
• Peptide bonds are aligned roughly parallel with the helical axis
• Side chains point out and are roughlyperpendicular with the helical axis
Left and right handedness
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• Not all polypeptide sequences adopt a helical structures
• Small hydrophobic residues such as Ala and Leu are strong helix formers
• Pro acts as a helix breaker because the rotation around the N-Ca bond is
impossible
• Gly acts as a helix breaker because the tiny R group supports other
conformations
Peptide dipole
Beta Sheet
• The backbone is more extended with the y dihedral
(N–Ca—C–N) in the range ( 90° < y < 180°)
• The planarity of the peptide bond and tetrahedral geometry of the a-carbon
create a pleated sheetlike structure
• Sheet-like arrangement of backbone is held together by hydrogen bonds
between the more distal backbone amides
• Side chains protrude from the sheet alternating in up and down direction
• Parallel or antiparallel orientation of two chains within a sheet are possible
• In parallel b sheets the H-bonded strands run in the same direction
• In antiparallel b sheets the H-bonded strands run in opposite directions
Beta strand is an extended structure… 3.5 A between R groups in sheet
compared to 1.5 in alpha helix
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Anti‐parallel B sheet
R‐groups spaced at 3.5 A
Distance
R groups alternate above
and below plane of sheet
Parallel B sheet
R‐groups spaced at 3.25 A
distance
R groups alternate above and
below plane of sheet
Parallel and antiparallel
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The Beta turn
• b-turns occur frequently whenever strands in b sheets change the
direction
• The 180° turn is accomplished over four amino acids
• The turn is stabilized by a hydrogen bond from a carbonyl oxygen to amide
proton three residues down the sequence
• Proline in position 2 or glycine in position 3 are common in b-turns
The Beta turn
Cis and Trans proline
Tertiary Structures
• Tertiary structure refers to the overall spatial arrangement of atoms in a
polypeptide chain or in a protein
• One can distinguish two major classes
– fibrous proteins
typically insoluble; made from a single secondary structure
– globular proteins
water-soluble globular proteins
lipid-soluble membrane proteins
Fibrous Proteins
Keratin
Hair
Collagen
Collagen
Silk
Silk
Globular Proteins
Myoglobin Tertiary
A simple motif
An elaborate motif
X-ray diffraction
NMR (1D)
NMR (2D)
Constructing large motifs
Quaternary structure
• Quaternary structure is formed by spontaneous assembly
of individual polypeptides into a larger functional cluster
• Oligomeric Subunits are arranged in Symmetric Patterns
Hemoglobin
Rotational symmetry
Dihedral symmetry
Protein Denaturation
Protein Denaturation
Protein Renaturation
Protein folding
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Folding pathway
Molten globules
Chaperones