4 | Proteins: Structure, Function, Folding
© 2013 W. H. Freeman and Company
CHAPTER 4
Lesson 1
– General aspects of protein structure
– The importance of non-covalent interactions in
protein structure
– Main characteristics and properties of the peptide
bond
– Ramachandran plots
Proteins:
Main Agents of Biological Function
• Catalysis
– enolase (in the glycolytic pathway)
– DNA polymerase (in DNA replication)
• Transport
– hemoglobin (transports O2 in the blood)
– lactose permease (transports lactose across the cell membrane)
• Structure
– collagen (connective tissue)
– keratin (hair, nails, feathers, horns)
• Motion
– myosin (muscle tissue)
– actin (muscle tissue, cell motility)
“Protein”
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One or more polypeptide chains
One polypeptide chain - a monomeric protein
More than one polypeptide chain- multisubunit/
multimeric protein (units α, β, γ…)
Subunits are identical-homomeric
Subunits are different-heteromeric
At least two of the subunits are the same
oligomeric and the subunits are known as
protomers
Proteins frequently contain other
groups in their structures
• Polypeptides (covalently linked α-amino acids) + possibly:
cofactors : required for protein activity, lightly bounded
− functional non-amino acid component
− can be metal ions or organic molecules
• coenzymes : required for enzyme activity
− organic cofactors
− ex: NAD+ in lactate dehydrogenase
• prosthetic groups
− Covalently/tightly attached non-amino acid
cofactors/coenzyme
• other modifications: amino acids may have post
translational or reversible modifications
•
Classes of Conjugated Proteins
Describing Hemoglobin
• Four subunits
• Heterotetrameric
• Two different chains/
protomers (α and β)
• two alpha oligomers
/chains and two beta
oligomers/chains 2α2β
• Prosthetic group: heme
• Conjugated protein:
hemoprotein
https://upload.wikimedia.org/wikipedia/common
s/thumb/3/3d/1GZX_Haemoglobin.png/800px1GZX_Haemoglobin.png
4 Levels of Protein Structure
Structure of Proteins
• Unlike most organic polymers, protein molecules
adopt a specific three-dimensional conformation.
• This structure gives the protein the ability to fulfill a
specific biological function
• This structure is called the native fold
• The native fold has a large number of favorable
interactions within the protein
• There is a cost in conformational entropy of folding
the protein into one specific native fold
Favorable Interactions in Proteins
• Hydrophobic effect
– Release of water molecules from the structured solvation layer around
the molecule as protein folds increases the net entropy
• Hydrogen bonds
– Interaction of N-H and C=O of the peptide bond leads to local regular
structures such as α-helices and β-sheets
• London dispersion
– Medium-range weak attraction between all atoms contributes
significantly to the stability in the interior of the protein
• Electrostatic interactions
– Long-range strong interactions between permanently charged groups
– Salt-bridges, esp. buried in the hydrophobic environment strongly
stabilize the protein
• Disulfide bridges
Peptide bond formation
Structure of the Peptide Bond
• Structure of the protein is partially dictated by
the properties of the peptide bond
• Compared to a simpler amide, peptide bonds:
– to be quite rigid and nearly planar
– to exhibit a large dipole moment in the
favored trans configuration
• The peptide bond is a resonance hybrid
of two canonical structures
Resonance in the Peptide Bond
The polypeptide is made up of a series of
planes linked at α carbons
The Rigid Peptide Plane and
the Partially Free Rotations
• Rotation around the peptide bond is not permitted
• Rotation around bonds connected to the alpha carbon
is permitted
• φ (phi): angle around the α-carbon—amide nitrogen
bond
• ψ (psi): angle around the α-carbon—carbonyl carbon
bond
• In a fully extended polypeptide, both ψ and φ are
180°
Distribution of φ and ψ Dihedral Angles
• Some φ and ψ combinations are very unfavorable because of
steric crowding of backbone atoms with other atoms in the
backbone or side chains
• Some φ and ψ combinations are more favorable because of
chance to form favorable H-bonding interactions along the
backbone
• A Ramachandran plot shows the distribution of φ and ψ
dihedral angles that are found in a protein
• shows the common secondary structure elements
• reveals regions with unusual backbone structure
Ramachandran Plot
Formation of peptide bonds
Which functional groups are used by α-amino
acids to form the peptide bond?
a. Hydroxyl and amino
b. α-Carboxylic acid and hydroxyl
c. α-Carboxylic acid and α-amino
d. Carboxylic acid and amino
Conformation of the peptide bond
The number of conformations found for the
peptide bond is limited to the cis or trans
conformations due to:
a. The number of amino acids in the peptide
or protein
b. The formation of hydrogen bonding
c. Restricted rotation around the peptide
bond
d. Steric hinderance
e. All of the above
Dihedral angles in peptides
The set of admissible values of the dihedral
angles φ (phi) and ψ (psi) in found naturally
in peptides and proteins is limited due to:
a. The number of amino acids in the peptide
or protein
b. The formation of hydrogen bonding
c. Restricted rotation around the peptide
bond
d. Steric crowding
e. All of the above