Transcript Prof. Kamakaka`s Lecture 3 Notes

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°
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Steric Hindrance
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
• 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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Folding pathway
Molten globules
Chaperones