B1.2 Proteins Flashcards
B1.2.1—Generalized structure of an amino acid
Students should be able to draw a diagram of a generalized amino acid showing the alpha carbon atom
with amine group, carboxyl group, R-group and hydrogen attached.
Amino acids have a central carbon atom with four
different atoms or groups linked to it:
R
H
amino acid
OH
* hydrogen atom
* amine group (-NH,)
* carboxyl group (-COOH)
* R-group (R)
Each of the 20 amino acids in proteins has a different
R-group.
B1.2.2—Condensation reactions forming dipeptides and longer chains of amino acids
Students should be able to write the word equation for this reaction and draw a generalized dipeptide
after modelling the reaction with molecular models.
Amino acids are linked together by condensation
reactions. The new bond formed between the amine
group of one amino acid and the carboxyl group of the
next is a peptide bond.
R R
H
\ //
— C
＼ N - C- C
ÓH OH
H
condensation reaction
between amino acids -> H20
H
peptide b o n d
A molecule consisting of two amino acids linked
N C C- Nー C
OH
H H
dipeptide
together is a dipeptide. Polypeptides consist of many
amino acids linked by peptide bonds.
B1.2.3—Dietary requirements for amino acids
Essential amino acids cannot be synthesized and must be obtained from food. Non-essential amino acids
can be made from other amino acids. Students are not required to give examples of essential and nonessential amino acids. Vegan diets require attention to ensure essential amino acids are consumed
All of the 20 amino acids that are used to
make polypeptides are produced in plants by
photosynthesis. These amino acids pass to animals
in their food. Animals can use metabolic pathways to
convert some amino acids into others-these are the
non-essential amino acids. An essential amino acid is
one that cannot be synthesized in sufficient quantities
by an animal so must be obtained from the diet.
Nine of the 20 amino acids are essential in humans. For
example, the amino acid phenylalanine is essential as it
cannot be synthesized by the human body but tyrosine
is non-essential as it can be made from phenylalanine.
Animal-based foods (fish, meat, milk, eggs) supply
amino acids in the proportions n e e d e d in the human
diet, but some plant-based foods have too little of
specific amino acids for human needs. For example,
cereals such as wheat have a low lysine content,
whereas peas and beans are low in methionine. Both of
these amino acids are essential in the human diet.
In a vegan diet attention must therefore be given to
ensure that enough of each essential amino acid is
consumed. Traditional plant-based diets in successful
civilizations have been found to provide such
a balance.
B1.2.4—Infinite variety of possible peptide chains
Include the ideas that 20 amino acids are coded for in the genetic code, that peptide chains can have any
number of amino acids, from a few to thousands, and that amino acids can be in any order. Students
should be familiar with examples of polypeptides.
A peptide is an unbranched chain of amino acids. If
there are between 2 and 10 amino acids, the chain
is an oligopeptide. If there are more than 20 amino
acids it is a polypeptide. There can be over 10,000
amino acids in a peptide chain-any number is
possible, though most polypeptides have between
50 and 2,000 amino acids.
The table shows some examples.
Peptide
Glucagon
Myoglobin
Titin
Amino acids Function
29
Glucose-release hormone
153
27-35,000
Oxygen storage in muscle
Elastic recoil in muscle
* Twenty amino acids are coded for in the genetic
code. The first amino acid in a peptide chain (and
every subsequent amino acid) can be any of these
20. If we consider a chain of 10 amino acids, the
number of possible sequences is 201° which is over
10 trillion. If we add all the possibilities for longer
amino acid sequences, the number of possible
peptide chains is effectively infinite.
* The amino acid sequence of a polypeptide is coded
for by a gene. The sequence of bases in the DNA of
the g e n e determines the s e q u e n c e of amino acids in
the polypeptide.
* O v e r two million p o l y p e p t i d e s have so far b e e n
identified in living organisms. This is only a small
proportion of the possible sequences. Other
sequences are either not useful or the gene for
making them has never evolved.
B1.2.5—Effect of pH and temperature on protein structure
Include the term “denaturation”.
Most proteins are delicate and their three-dimensional
shape is easily damaged by changes to chemical or
physical conditions. This is called denaturation.
1. Heat causes vibrations
within protein molecules
that b r e a k intramolecular
bonds and cause the
conformation to change.
H e a t d e n a t u r a t i o n is a l m o s t
always irreversible. This
can be demonstrated by
heating egg white, which
contains dissolved albumin proteins. The albumins are
denatured by the heat and in their new conformations
are insoluble. This causes the liquid egg white to turn
into a white solid.
2. Every protein has an
ideal or optimum pH at
which its conformation
is normal. If the pH is
increased by adding
alkali or d e c r e a s e d
by adding acid, the
conformation of the
protein may initially stay the same but denaturation
occurs when the pH has deviated too far from the
optimum. This is because the pH change causes
intramolecular bonds to break within the protein
molecule. The photograph shows egg white mixed
with hydrochloric acid.
B1.2.6—Chemical diversity in the R-groups of amino acids as a basis for the immense diversity in protein
form and function
Students are not required to give specific examples of R-groups. However, students should understand
that R-groups determine the properties of assembled polypeptides. Students should appreciate that Rgroups are hydrophobic or hydrophilic and that hydrophilic R-groups are polar or charged, acidic or basic
Of the four groups linked to the central carbon of an
amino acid, the amine an d carboxyl g r o u p s are used to
form peptide bonds and the hydrogen atom has little
influence, so it is the R-groups of the amino acids in
peptide chains that largely determine the properties of
proteins. They are very diverse in their chemical nature.
* Half of the R-groups are hydrophobic, some with
rings of atoms and one (methionine) containing
sulfur. These hydrophobic R-groups are more
attracted to each other than to the other half of the
R-groups which are hydrophilic.
* About a third of the hydrophilic R-groups are polar
but do not ionize. They can form hydrogen bonds
with other R-groups.
* Another third of the hydrophilic R-groups have an
amine group that can accept a proton, so they are
basic. The extra proton makes the R-group positively
charged.
* The other third of the hydrophilic R-groups can
donate a proton, so they are acidic. Loss of a proton
makes them negatively charged, so they can also
form ionic bonds with positively charged R-groups.
* One R-group is mildly hydrophilic and contains
an -SH group. Pairs of these R-groups can form a
covalent S-S bond called a disulfide bridge.
* Both hydrophobic and hydrophilic R-groups vary in
size, ranging from glycine with just a single hydrogen
atom, to tryptophan which is the largest. They also
differ in shape, some having unbranched or branched
chains of atoms and others having rings.
B1.2.7—Impact of primary structure on the conformation of proteins
Students should understand that the sequence of amino acids and the precise position of each amino acid
within a structure determines the three-dimensional shape of proteins. Proteins therefore have precise,
predictable and repeatable structures, despite their complexity.
Protein conformations are most easily understood by recognizing four levels of structure, from primary to quaternary. Primary structure is the number and sequence of amino acids in a polypeptide.
The conformation of a molecule is the arrangement of its atoms in space. In carbon compounds there can be changes of conformation due to bond rotation, giving alternative structures for the same compound.
Cells construct proteins with each amino acid in a precise position, so the overall conformation of the protein is predictable and repeatable. Software has been developed (for example, AlphaFold) for predicting these conformations from amino acid sequences but even with powerful computers, predicted conformations are sometimes found to be false.
As a polypeptide is synthesized by a ribosome, from the N-terminal to the C-terminal, it gradually develops its conformation, guided by the chemical properties of each amino acid added. Parts of the chain may coil up to form a helix and, at particular points, folds may form to make the shape globular. Every time a polypeptide with a particular sequence of amino acids is synthesized on a ribosome, its conformation will tend to be precisely the same. It is stabilized by intramolecular bonds between the amino acids brought together by the coiling and folding processes.
The primary structure of beta-endorphin is a sequence of 31 amino acids (right), which determines the distinctive conformation of this small polypeptide, allowing it to bind to opioid receptors and thus act as a neurotransmitter in the orain.
B1.2.8—Pleating and coiling of secondary structure of proteins
Include hydrogen bonding in regular positions to stabilize alpha helices and beta-pleated sheets.
When amino acids are linked together by peptide bonds,
a repeating sequence of covalently bonded carbon and
nitrogen atoms is formed: N-C-C-N-C-C-This forms the
strong backbone of the polypeptide.
Each nitrogen atom in the repeating sequence has a
hydrogen bonded to it (N-H) and every second carbon
atom has an oxygen atom double bonded to it (C=O).
Hydrogen bonds can form between the N-H and
C = 0 groups in a polypeptide if they are brought close
together. For example, if sections of polypeptide run
alpha helix
HO
hydrogen ribbon model of polypeptide
(bond showing secondary structures
parallel, hydrogen bonds can form between them. The
Adapted from Fokine et al (2013).
The molecular architecture
of the bacteriophage T4
structure that develops is called a beta-pleated sheet.
neck. Journal of Molecular
Biology, 425(10), 1731-1744.
doi:10.1016/i.imb.2013.02.012
If the polypeptide is wound into a right-handed helix,
h y d r o g e n b o n d s c a n form b e t w e e n a d j a c e n t turns of t h e
helix. The structure that develops is called an alpha helix. Because the groups forming hydrogen bonds are
beta-pleated sheet
C-C-N
regularly spaced, these helices and sheets always have
the same dimensions.
Alpha helices and beta-pleated sheets stabilized by
hydrogen bonding are the secondary structure of a polypeptide
B1.2.9—Dependence of tertiary structure on hydrogen bonds, ionic bonds, disulfide covalent bonds and
hydrophobic interactions
Students are not required to name examples of amino acids that participate in these types of bonding,
apart from pairs of cysteines forming disulfide bonds. Students should understand that amine and
carboxyl groups in R-groups can become positively or negatively charged by binding or dissociation of
hydrogen ions and that they can then participate in ionic bonding.
Tertiary structure is the three-dimensional conformation of a polypeptide. It is formed when a polypeptide folds up after being produced by translation. The conformation is stabilized by intramolecular bonds and interactions that form between amino acids in the polypeptide, especially between their R-groups.
Intramolecular bonds can form between amino acids widely separated in the primary structure but brought together during the folding process. ionic bonds can form between positively a and negatively charged R-groups
There are four main types of interaction:
* hydrogen bonds where two polar R-groups interact
* ionic bonds between NH+ and COO groups
* disulfide bonds-sulfur-sulfur covalent bonds which can only form where two cysteines come together
* hydrophobic interactions-the weakest type of interaction that forms between two or more non-polar
R-groups.
acidic amino acids have R-groups that can lose an H* ion and so become negatively charged
HO
basic amino, acidshave
R-groups that
العبات االجية
an Hion and so become positively charged
H
月-
H
-N*
soleucirte
a sausage model showing the tertiary structure of lysozyme (an enzyme in tears)
Arginine
Asparagine
disulfide
bridges, which are strong covalent
$
bonds, can form between pairs → of cysteines
季
入
Methionine;
Serine
H
N
H CHг
H
Valine
hydrophobic interactions, which are weak bonds, can form between R-groups that are non-polar including all those projecting inwards here
hydrogen bonds can form between some R-groups
B1.2.10—Effect of polar and non-polar amino acids on tertiary structure of proteins
In proteins that are soluble in water, hydrophobic amino acids are clustered in the core of globular
proteins. Integral proteins have regions with hydrophobic amino acids, helping them to embed in
membranes.
Proteins with hydrophilic (polar) amino acids on their outer surface tend to dissolve in water. They often have hydrophobic (non-polar) amino acids in their core. This arrangement stabilizes the protein’s tertiary structure in aqueous solutions.
Proteins with hydrophobic amino acids on their outer surface are attracted to the non-polar core of membranes, so they become integral membrane proteins. The diagram shows how they can adopt a variety of positions depending on the distribution of polar and non-polar amino acids on their surface.
hydrophilic exterior of water-soluble protein
hydrophobic core of water-soluble protein
The distribution of polar and non-polar amino acids determines the tertiary structure of proteins and also where they are located in cells. Many proteins are water-soluble so remain dissolved in the cytoplasm or in aqueous solutions inside organelles. There are also many proteins that are an integral part of membranes.
hydrophobic parts of membrane proteins are embedded in the membrane
hydrophilic parts of membrane proteins protrude
B1.2.11—Quaternary structure of non-conjugated and conjugated proteins
Include insulin and collagen as examples of non-conjugated proteins and haemoglobin as an example of a
conjugated protein.
NOS: Technology allows imaging of structures that would be impossible to observe with the unaided
senses. For example, cryogenic electron microscopy has allowed imaging of single-protein molecules and
their interactions with other molecules.
Some proteins contain a non-polypeptide structure called a prosthetic group. They are known as conjugated proteins. Haemoglobin is an example as the haem groups are not polypeptides.
Quaternary structure is the linking of two or more polypeptides to form a single protein. The same types of alpha chains beta chains
intramolecular bonding are used as in tertiary structure.
Goodsell, D. S. (2004).
Carbonic anhydrase. RCSB
there is a haem group in each haemoglobin polypeptide (two shown here)
Protein Data Bank. doi: 10.2210/ resb_pdb/mom_2004_1
B1.2.12—Relationship of form and function in globular and fibrous proteins
Students should know the difference in shape between globular and fibrous proteins and understand that
their shapes make them suitable for specific functions. Use insulin and collagen to exemplify how form
and function are related.
Form and function are closely related in proteins. Fibrous
Insulin is a globular protein that functions as a hormone.
proteins have unfolded polypeptides, so are narrow and
elongated. They have structural roles within and between
Small size and a hydrophilic surface allows molecules of
insulin to be carried dissolved in blood plasma. Insulin’s
cells. Globular proteins have folded polypeptides and
therefore a rounded shape. Their varied shapes allow them
distinctive shape allows it to bind to a site on a specific
receptor protein, located in the plasma membrane of
to have many roles in cells.
Collagen is a fibrous protein.
Its three polypeptides are more
elongated than alpha helices,
so they can be wound together
target cells. insulin on hydrophobic
the binding alpha helices
site of the embedded
r e c e p t o r
4 in plasma
m e m b r a n e
insulin’s
into a triple helix. Like a rope,
collagen can withstand pulling
forces (tensions) by stretching
rather than breaking. Collagen
is produced by fibroblasts and
released into the extracellular
matrix of tissues where tensile
strength is needed in skin,
A-chain has
21 amino
acids
the B-chain has 30 amino acids; the A
and B chains are made as a 110-amino
and cross-linked by disulfide bonds; a
middle section is then removed
acid-long polypeptide which is folded
inner parts of receptor that pass
bones, tendons, and ligaments.
the signal to the cytoplasm
Adapted from RCSB Protein Data Bank
stretching under tension
recoil
collagen has three polypeptides with an amino acid
sequence that prevents formation of alpha helices, so the
chains can be wound together into a rope-like conformation
