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BIOL 200 (Section 921)
Lecture # 2, June 20, 2006
• Reading for lecture 2: Essential Cell Biology (ECB) 2nd
edition. Chap 2 pp 55-56, 58-64, 74-75; Chap 4, pp.
119-143. Good questions: 4-3, 4-10G, 4-11, 4-14-15, 417.
• Learning Objectives
1. Understand how amino acids are joined together via
peptide bonds to form a polypeptide. Be able to write out
the structure of the reactants and the product.
2. Recognize the properties of each of the 20 amino acids,
their three letter abbreviations, and how they are linked
by peptide bonds.
Chemical nature of amino
acids?
Abbreviations and side chain polarity of
twenty amino acids
Basic side chains-positively charged
Panel 2-5, p74
at physiological pH
Panel 2-5, p75
Acid side chainsnegatively charged
Panel 2-5, p75
Polar side chains-interact
well with water, can form
H-bonds
Panel 2-5, p75
Nonpolar groups-energetically
unfavorable for them to contact water
Amino acids are linked together by covalent
peptide bonds (Fig. 4-1)
Proteins are made up of a polypeptide backbone with
attached side chains
(Fig. 4-2)
Characteristics of Polypeptide synthesis
• The amino group of one amino acid reacts with the
carboxyl group of another to form a peptide bond
(=amide linkage) with the elimination of a water
molecule.
• The polarity of the molecule is retained. The monomers
are all joined together in the same orientation. The
polypeptide chain has polarity.
• The polypeptide contains a free amino group at one end
and a free carboxyl group at the other. These ends of the
polypeptide chain are referred to as the amino and
carboxyl termini (ends) respectively.
• The product of the condensation reaction preserves the
reactive group (carboxyl group) at the end of the
molecule. This makes it possible for the peptide chain to
join to yet another amino acid.
The four levels of organization of protein structure
[Lehninger et al. Principles of Biochemistry]
•
•
•
•
The primary structure of protein: a sequence of amino acids linked
together by peptide bonds (covalent bond)
The secondary structure of protein: Polypeptide folding into α helix, β
sheet, or random coil (H bonds involved)
The tertiary structure of protein: 3-D folding of a single polypeptide chain
(H bonds, disulfide bonds, ionic bonds, van der Waals interactions,
hydrophobic interactions)
The quaternary structure of proteins: Association of two or more folded
polypeptides (sub units) to form a multimeric protein (bonds and
interactions similar to tertiary structure)
Unity and diversity of proteins
Primary structure (sequence of amino acids)
determines the structure of a protein
Fig.4-5: In water, hydrophobic aa cluster inside a folded
protein, away from solvent. Why?
Secondary structure of proteins -  helix
H bond between the N-H of every peptide bond to the C=O of the next
peptide bond of the same chain. R groups are not involved.
(e.g. in protein -keratin - abundant in skin, hair, nails and horns)
[Fig. 4-10, p. 128]
(Pitch)
Secondary structure of proteins – β sheet
Polypeptide chains are held together by H bonds between N-H group of
one polypeptide chain and C=O group of the other chain
(e.g. in the protein fibroin - abundant in silk) [Fig. 4-10, p. 128]
helices can wrap around one another by interactions
between their hydrophobic side chains to form a stable
coiled-coil. [Fig. 4-16]
e.g.  keratin in the skin and myosin in muscles
Tertiary structure of proteins
• 3D conformation or shape
• Depends on the properties of the R groups
of amino acid residues
• Fold spontaneously or with the help of
molecular chaperones
• Stabilized by covalent and non-covalent
bonds
Many proteins are composed of separate
functional domains e.g. bacterial catabolite protein (CAP).
Protein domain: a segment (100 – 250 aa) of a polypeptide chain that
fold independently into a stable structure [Fig. 4-19]
Noncovalent bonds help protein folding (Fig. 4-4)
Also review Panel 2-7 (pp. 78,79) on noncovalent bonds
Covalent disulfide bonds between adjacent
cysteine side chains help stabilize a favored
protein conformation [Fig. 4-29]
Molecular chaperone proteins assist folding
of other proteins
[Horton et al. Principles of Biochemistry, 2nd ed.]
How is the tertiary structure of a
polypeptide chain stabilized?
• Ionic bonds (usually between charged amino acid side
chains at cellular pH 7.0) (Fig. 4-4) (eg. Lys-NH3
+ and Asp-COO-)
• Hydrogen bonds between R groups (remember
uncharged polar amino acids can H-bond!!! –Ser-OH,
Thr-OH and Tyr-OH with for example Glu=O or Gln=O)
• Covalent bonds (disulfide bonds between cysteines, see
Fig. 4-29)
• Hydrophobic interactions-non-polar side chains
associate in the interior of the molecule and exclude
water) (Fig. 4-5)
• van der Waals interactions
Quaternary structure of proteins: hemoglobin, a
protein in red blood cells, has four sub units (two
copies each of - and β-globins containing a heme
molecule [Fig. 4-23].
Gel electrophoresis method is used to separate proteins
[Lehninger et al. Principles of Biochemistry]
Problem Solving: Shown in the table below are the
sequences of selected amino acids from different types of
human hemoglobin (abbreviated Hb). Some forms of
hemoglobin are defective, while others are not. From what you
know about protein structure, explain why Sickle Cell and
Hammersmith Hbs are defective while delta Hb is not.
Amino acid number
Type of Hemoglobin (Hb)
3
4 5 6.. 9... 40 41 42 43
Normal beta Hb
Leu Thr Pro Glu Ser Gln Arg Phe Glu
Sickle Cell Hb (defective)
Leu Thr Pro Val Ser Gln Arg Phe Glu
Hammersmith Hb (defective)
Leu Thr Pro Glu Ser Gln Arg Ser Glu
Normal delta Hb
Leu Thr Pro Glu Thr Gln Arg Phe Glu