Proteins Structure and

Function

By Biological Science
Chapter 3 Opening Roadmap.
Introduction
§ Amino acids are the building blocks of proteins

§ Could a protein have been the initial spark of life?

 Amino Acids
What is for?

PROTEINS ARE THE MOST ABUNDANT AND

FUNCTIONALLY DIVERSE MOLECULES!

§ Forming parts of coenzymes

§ Precursors for the biosynthesis of molecules such

as heme, GABA, some hormones…
Functions of Proteins
 Structure of the Amino Acids
(Very important!)
Each amino acid has:

§ All are bonded to the α-carbon

atom.

§ These carboxyl and amino

groups are combined in peptide
linkage.
The Structure of Amino Acids
§ In water, the amino and carboxyl groups ionize to
NH3+ and COO–, respectively

Amino Carboxyl
group group

Side
chain
 Optical Properties of A.A.

§ Configuration: Chiral molecule

Ø if a molecule has an atom bonded to
four different groups, is called as
chiral (asymmetric).

Ø Glycine is the exception.

 Amino acids:Chirals
§ Enantiomers: a chiral molecule,
has left- and right-handed
isomers, called enantiomers

§ Designated in two forms: D and L, that are mirror

images of each other
The name and Abbreviations of A.A.s

§ All the AAs were given a

trivial name

§ Each AA is given a 3 letter

abbreviation and 1 letter
symbol
Classification of Amino Acids
According to their R group (Based on polarity)

1)Nonpolar (hydrophobic): Nonpolar Polar

apolar side chain
2)Polar (hydrophilic): polar
and uncharged side chain
3)Acidic (hydrophilic):
negatively charged side Acidic Basic
chain
4)Basic (hydrophilic):
positively charged side
chain (-NH2)
1)Nonpolar Side Chains
§ R group can be: H atom, an alkyl group or an
aromatic ring such as proline
§ They have non-polar side that does not participate
in ionic or hydrogen bonding
Nonpolar Side Chains

§ The side chains can act as lipid-like

 Nonpolar Side Chains
§ Glycine
Ø R group is H
Ø Symmetric not chiral

§ Proline
Ø Imino acid
Ø Five-membered ring
structure, rigid in
conformation
Ø Secondary amino group
2) Uncharged Polar Side Chains

§ R group: More hydrophilic because they form

hydrogen bonds with water
Ø Hydroxyl groups
Ø Sulfur atoms
Ø Amide groups
Disulfide bonds
ØDisulfide bonds: stabilise proteins by forming covalent
links

disulfide
bond
 3)Acidic Side Chains

§Have a negatively charged

carboxylate group (COO-)
at physiologic pH
 4)Basic side chains
§ Proton acceptors
At physiological pH,
Ø Lysine and Arginine:
protonated
Ø Histidine: weakly basic
and free amino acid is
largely uncharged
 The Polarity and Charge of R-Groups
Affect Solubility
1. Does the side chain have a negative charge?
2. Does the side chain have a positive charge?
3. If side chain is uncharged, does it have an
oxygen atom?

§ If the answers to all three questions are NO

§ Then it is a nonpolar amino acid
 Aromatic Amino Acids

• The -OH group in Tyr is an important functional group in

proteins (phosphorylation, hydrogen bond, etc), polar
Aromatic AAs are responsible for the light absorption of
proteins at 280 nm

•Proteins in solution absorb

UV light with absorbance
maximum at 280nm

•Measuring protein content

by spectrophotometer
Special Amino Acids
(Important)
•Glycine: Side chain is –H, very flexible
Not chiral

•Proline: Two covalent bonds with backbone, rigid

Amino group is secondary

§Cysteine can form disfulfide bridge to stabilize structure

Classification of Amino Acids
Based on nutritional requirements

A)Essential amino acids

§ Their carbon skeleton cannot be synthesized by
the humans, must be supplied in the diet
 Essential and non-essential amino acids

B)Semi-essential amino acids:

§Required by growing children/pregrant in food
§2: His and Arg

C)Non-essential amino acids:

§The remaining 10 amino acids are non-essential, because their
carbon skeleton can be synthesized by the body
 pH and Ionization
§ In neutral solution (pH 7.0), the amino acid contains a negative
charge and a positive charge. It is called a zwitterion (German
for “hybrid ion”)

pH<pI pH=pI pH>pI

§ The point at which an AA has equal positive and negative charges:

isoelectic point (pI)
 How Do Amino Acids Link to Form
Proteins?
§ Proteins are macromolecules
§ Subunits are called monomers
§ Monomers link together to form polymers

Growing polymer
Polymerization
(bonding together
of monomers)

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Polymerization of Proteins in Early Earth

§ Monomers polymerize through condensation

(dehydration) reactions
§ Hydrolysis is the reverse reaction

§ During chemical evolution, polymerization would

occur only if the amino acid concentration was
very high
 Peptide Bond
The amide bond between the carboxyl group of one
amino acid and the -amino group of another

Amino acid
residue

peptide bond
 Amino acids joined by peptide bond
N-terminus C-terminus
Peptide-
bonded
backbone

Amino Carboxyl
group group

One of the nine

amino acid
residues in this
chain Carboxyl
group
Amino Peptide
group bond

Chains flex because groups on

either side of each peptide bond
can rotate about their single bonds

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 Polymers of amino acids

§ Dipeptide: 2 amino acid residues, tripeptide: 3

residues, and so on
§ Oligopeptide: 12~20 residues
§ Polypeptide: many residues
Key Points
§ General structure of a-amino acids
§ Chiral, D- and L-forms of AAs
§ The Classification of Amino Acids
§ Nonpolar, uncharged polar, acidic and basic
§ Essential amino acids
§ Zwitterion, pI
§ Characteristics of the peptide bond
 What Do Proteins Look Like?
§ Proteins have unparalleled diversity of size, shape,
and chemical properties
(a) Collagen Triple strands

Fibrous; provides structural support

(b) TATA box–binding protein (c) Porin (d) Chymotrypsin

Saddle-shaped; Doughnut-shaped; Globular; binds
binds DNA (DNA forms a pore substrates Target
shown in shades protein
of red)

Target
DNA
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What Do Proteins Look Like?
§ All proteins have just four basic structures:
1. Primary
2. Secondary
3. Tertiary
4. Quaternary
Primary Structure
§ Protein primary structure is its unique sequence of
amino acids
§ Primary structure is fundamental to the higher
levels of protein structure
Insulin
 (a) Normal sequence of residues

5 6 7

Sickle Cell
Normal
red blood
cells

Anemia
(b) Single change in sequence of
residues

5 6 7

Sickled
red blood
cell

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Secondary Structure
§ Protein secondary structure is formed by
hydrogen bonds between
§ The carbonyl group of one amino acid
§ The amino group of another amino acid
 (a) Hydrogen bonds can form between nearby amino
and carbonyl groups on the same polypeptide chain.

(b) Secondary structures of proteins result.

Types of
secondary
structure:
α helix
α-helix β-pleated sheet

(c) Ribbon diagrams of secondary structure

Arrowheads
point toward
the carboxyl end
of the primary
structure

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α-helix β-pleated sheet
Cell Biology Video: An Idealized Alpha
Helix
Types of secondary structure:
β pleated sheet
Tertiary Structure
§ The overall three-dimensional structure of a
polypeptide is called its tertiary structure
§ The tertiary structure of a polypeptide results
from
§ Interactions between R-groups
§ Or between R-groups and the peptide backbone
 (a) Interactions that determine the tertiary structure of proteins

Hydrogen bond
between side chain and
carbonyl group on
backbone Ionic bond

Hydrophobic
interactions Disulfide bond
Hydrogen bond
+
between two side chains
van der Waals
interactions

(b) Tertiary structures are diverse.

A tertiary
structure
composed
mostly of
β-pleated
sheets
A tertiary A tertiary
structure structure
composed rich in
mostly of disulfide
α-helices bonds

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 Quaternary Structure
§ Many proteins contain several distinct polypeptide subunits
that interact to form a single structure
§ The bonding of two or more distinct polypeptide subunits
produces quaternary structure

(a) Cro protein, a dimer (b) Hemoglobin, a tetramer

α1 α2

β1 β2

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Summary
 Folding and Function
§ Protein structure is hierarchical
§ All of the higher-level structures are based on
primary structure
 Ribonuclease protein, folded Ribonuclease protein, denatured (unfolded)

HS
Denaturant added

S
S Denaturant removed HS
S S HS
HS

Disulfide S
S
bonds

HS
HS

HS
S HS
S Hydrogen
bonds
Broken disulfide and
hydrogen bonds

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 Denaturation

Alternations in pH, salt concentration, temperature, or

other environmental factors
When a protein loses its higher-order structure, but not
its primary sequence, this loss of a protein’s native
conformation is called denaturation
Denaturation

Normal protein Denatured protein

Renaturation
 Folding Can Be “Infectious”
§ Misfolding can be “infectious”
§ A prion is a type of protein that can trigger
normal proteins in the brain to fold abnormally-
Creutzfeldt-Jakob disease (CJD).

(a) Normal
(b) Infectious
prion protein
prion protein

α-helixes

in normal prion
β-pleated sheet in

Infectious prion
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 Protein Functions Are as Diverse as
Protein Structures
§ Proteins are crucial to most tasks required by cells
§ Catalysis
§ Defense
§ Movement
§ Signaling
§ Structure
§ Transport
Why Are Enzymes Good Catalysts?

A triad of key
residues (*) can
cut a substrate
like molecular
scissors
Protein
substrate
* Active
*
* site
Did life arise from a self-
replicating enzyme?