2.

4: Proteins
Amino Acids

Proteins are comprised of long chains of recurring monomers called amino

acids
Amino acids all share a common basic structure, with a central carbon atom
bound to:
o An amine group (NH2)
o A carboxylic acid group (COOH)
o A hydrogen atom (H)
o A variable side chain (R)
There are 20 different amino acids which are universal to
all living organisms
o A further two selenocysteine and pyrrolysine
are modified variants found only in certain
organisms
Amino acids are joined together on the ribosome to form long chains called
polypeptides, which make up proteins
Each type of amino acid differs in the composition of the variable side chain
o These side chains will have distinct chemical properties (e.g. charged,
non-polar, etc.) and hence cause the protein to fold and function
differently according to its specific position within the polypeptide
chain
As most natural polypeptide chains contain between 50 2000 amino acid
residues, organisms are capable of producing a huge range of possible
polypeptides
Peptide Bonds

Amino acids can be covalently joined together in a condensation reaction to

form a dipeptide and water
o The covalent bond between the amino acids is called a peptide
bond and, for this reason, long chains of covalently bonded amino
acids are called polypeptides
Polypeptide chains can be broken down via hydrolysis reactions, which
requires water to reverse the process
Formation of a Dipeptide

Peptide bonds are formed between the

amine and carboxylic acid groups of
adjacent amino acids
o The amine group loses a hydrogen
atom (H) and the carboxylic acid
loses a hydroxyl (OH) this forms water (H2O)
Molecular Diagram of a Peptide Bond
Protein Structure

Amino acids are covalently joined via peptide bonds to form long chains
called polypeptides
The order of the amino acid sequence is called the primary structure and
determines the way the chain will fold
o Different amino acid sequences will fold into different configurations
due to the chemical properties of the variable side chains
Amino acid sequences will commonly fold into two stable configurations,
called secondary structures
o Alpha helices occur when the amino acid sequence folds into a coil /
spiral arrangement
o Beta-pleated sheets occur when the amino acid sequence adopts a
directionally-oriented staggered strand conformation
Both -helices and -pleated sheets result from hydrogen bonds forming
between non-adjacent amine and carboxyl groups
o Where no secondary structure exists, the polypeptide chain will form a
random coil
Secondary Structure Alpha Helices versus Beta Pleated Sheets

The overall three-dimensional configuration of the protein is referred to as

the tertiary structure of the protein
The tertiary structure of a polypeptide chain will be determined by the
interactions between the variable side chains
o These interactions may include hydrogen bonds, disulphide bridges,
ionic interactions, polar associations, etc.
The affinity or repulsion of side chains will affect the overall shape of the
polypeptide chain and are determined by the position of specific amino acids
within a sequence
o Hence, the order of the amino acid sequence (primary structure)
determines all subsequent levels of protein folding
 Protein Folding: Primary Secondary Tertiary

Certain proteins possess a fourth level of structural organization called

a quaternary structure
Quaternary structures are found in proteins that consist of more than
one polypeptide chain linked together
Alternatively, proteins may have a quaternary structure if they include
inorganic prosthetic groups as part of their structure
Not all proteins will have a quaternary structure many proteins consist of a
single polypeptide chain
Quaternary Structure of a Protein

An example of a protein with a quaternary structure is haemoglobin

(O2 carrying molecule in red blood cells)
o Haemoglobin is composed of four polypeptide chains (two alpha
chains and two beta chains)
o It is also composed of iron-containing haeme groups (prosthetic
groups responsible for binding oxygen)
Denaturation

Denaturation is a structural change in a protein that results in the loss

(usually permanent) of its biological properties
o Because the way a protein folds determines its function, any change or
abrogation of the tertiary structure will alter its activity

Denaturation of proteins can usually be caused by two key conditions

temperature and pH
Denaturation of a Protein

Temperature
High levels of thermal energy may disrupt the hydrogen bonds that
hold the protein together
As these bonds are broken, the protein will begin to unfold and lose its
capacity to function as intended
Temperatures at which proteins denature may vary, but most human
proteins function optimally at body temperature (~37C)
pH

Amino acids are zwitterions, neutral molecules possessing both

negatively (COO) and positively (NH3+) charged regions
Changing the pH will alter the charge of the protein, which in turn will
alter protein solubility and overall shape
All proteins have an optimal pH which is dependent on the environment
in which it functions (e.g. stomach proteins require an acidic
environment to operate, whereas blood proteins function best at a
neutral pH)
Gene Polypeptide

A gene is a sequence of DNA which encodes a polypeptide sequence

A gene sequence is converted into a polypeptide sequence via two processes:
o Transcription making an mRNA transcript based on a DNA template
(occurs within the nucleus)
o Translation using the instructions of the mRNA transcript to link
amino acids together (occurs at the ribosome)
Typically, one gene will code for one polypeptide however there are
exceptions to this rule:
o Genes may be alternatively spliced to generate multiple polypeptide
variants
o Genes encoding tRNA sequences are transcribed but never translated
o Genes may be mutated (their base sequence is changed) and
consequently produce an alternative polypeptide sequence
The One Gene One Polypeptide Rule
Proteome

The proteome is the totality of proteins expressed within a cell, tissue or

organism at a certain time
o The proteome of any given individual will be unique, as protein
expression patterns are determined by an individuals genes
The proteome is always significantly larger than the number of genes in an
individual due to a number of factors:
o Gene sequences may be alternatively spliced following transcription to
generate multiple protein variants from a single gene
o Proteins may be modified (e.g. glycosylated, phosphorylated, etc.)
following translation to promote further variations
Formation of the Proteome
 Protein Functions
Proteins are a very diverse class of compounds and may serve a number of different
roles within a cell, including:

Structure e.g. collagen, spider silk

Hormones e.g. insulin, glucagon
Immunity e.g. immunoglobulins
Transport e.g. haemoglobin
Sensation e.g. rhodopsin
Movement e.g. actin, myosin
Enzymes e.g. Rubisco, catalase

Mnemonic: SHITS ME
The following are specific examples of the different functions of proteins:
Structure
Collagen: A component of the connective tissue of animals (most abundant
protein in mammals)
Spider silk: A fiber spun by spiders and used to make webs (by weight, is
stronger than kevlar and steel)

Hormones
Insulin: Protein produced by the pancreas and triggers a reduction in blood
glucose levels
Glucagon: Protein produced by the pancreas that triggers an increase in
blood glucose levels

Immunity
Immunoglobulins: Antibodies produced by plasma cells that are capable of
targeting specific antigens

Transport
Haemoglobin: A protein found in red blood cells that is responsible for the
transport of oxygen
Cytochrome: A group of proteins located in the mitochondria and involved in
the electron transport chain

Sensation
Rhodopsin: A pigment in the photoreceptor cells of the retina that is
responsible for the detection of light

Movement
Actin: Thin filaments involved in the contraction of muscle fibres
Myosin: Thick filaments involved in the contraction of muscle fibres

Enzymes
Rubisco: An enzyme involved in the light independent stage of
photosynthesis
Fibrous Vs. Globular Proteins
There are two main classes of protein tertiary structure:
Fibrous proteins are generally composed of long and narrow strands and have
a structural role (they are something)
Globular proteins generally have a more compact and rounded shape and
have functional roles (they do something)
Differences Between Fibrous and Globular Proteins

Mnemonic: SPADES