Protein Roles
1. Many proteins function as enzymes, the biochemical catalysts. Enzymes
catalyse nearly all reactions that occur in living organisms.
2. Some proteins bind other molecules for storage and transport. For
example, myoglobin binds oxygen in skeletal and cardiac muscle cells, and
haemoglobin binds and transports oxygen and carbon dioxide in red blood
cells.
3. Some proteins, such as tubulin, actin and collagen provide support and
shape to cells and hence to tissues and organisms.
4. Assemblies of proteins can do mechanical work, such as the movement of
flagella, the separation of chromosomes at mitosis and the contraction of
muscles.
5. Many proteins play a role in decoding information in the cell. Some are
involved in translation, whereas others play a role in regulating gene
expression by binding to nucleic acids.
6. Some proteins are hormones, which regulate biochemical activities in target
cells or tissues; other proteins serve as receptors for hormones.
7. Some proteins have highly specialised functions. For example, antibodies
defend vertebrates against bacterial and viral infections, and toxins, produced
by bacteria, can kill larger organisms.
These roles fall into four major functional groups:
Binding carrier protein or enzyme bind a ligand or a substrate. Nearly all
proteins have a binding function
Catalysis enzymes
Switching many proteins, especially in cell membranes, that bind things
that come from the outside of the cell. Receptors then change shape and
contact something inside the cell which switching something on inside the
cell which sends a signal to the nucleus
Structural hold cells in 3d shape
a central carbon
an amino group
an carboxylate group
a hydrogen atom
an R group
proton they are charged (although the charges cancel each other out) and are
therefore zwitterions.
Some R groups are also capable of being ionised. This is important in the role of
R groups in protein structure and function. For example, histones bind DNA
because DNA is strongly negatively charged and histones contain a lot of
lysine which is a basic amino acid it has a side chain that is positively
charged at pH 7 so the positive charge of the histone binds the negative charge
of the DNA.
These are:
GLYCINE
ALANINE
VALINE
LEUCINE
ISOLEUCINE
These amino acids build in complexity. The simplest is glycine and it has a very
important role to play in proteins. It is very small so is found at points in the
polypeptide where there is a turn. Small amino acids such as glycine are found
in these regions as large amino acids with bulky side chains would restrict the
ability of the protein to turn. All these amino acids, particularly the larger ones
(with longer hydrocarbon side chains) are hydrophobic. So, if there was a
stretch of these amino acids in the primary sequence of a protein, and the
protein folded up, these would be found on the inside of the protein, away from
the water. If they were on the outside of a protein, they could be forming a
binding site for something else that is hydrophobic.
Because both the and carbon atoms of isoleucine are asymmetric it has two
chiral centres and therefore four possible stereoisomers:
These are:
ASPARTATE
GLUTAMATE
ASPARGINE
GLUTAMINE
Aspartate and glutamate confer negative charge on proteins because their
side chains are ionised at pH 7. Under physiological conditions acidic side
chains exist as the conjugate base, hence the suffix
-ate.
These amino acids have either acidic side chains or polar side chains. Aspartate
and glutamate have a tendency to lose an electron so they are negatively
charged at pH 7. This means they are basic at pH 7. If there is one of these
groupings in the active site of an enzyme it acts as a base it would want to
grabs protons back or attract a positive charge. It could also be involved in base
catalysis where it abstracts a proton from something to make that group
nucleophilic so it can attack a susceptible bond. If there is an appropriately
positioned basic group next to water, it can take one of the protons from water,
forming the nucleophile OH-.
Asparagine and glutamine are not charged they are polar and can form
hydrogen bonds. This means they are very important structurally they can
form hydrogen bonds to other groups, forming a network. A single hydrogen
bond is very weak, but hundreds become a significant force.
Amino Acids with Basic R Groups
These are:
HISTDINE
LYSINE
ARGININE
The side chains of both lysine and arginine are positively charged at
physiological pH contributing basicity to proteins, arginine is the most basic of
the 20 amino acids.
They are positively charged because they have a pK which is higher than the pH
at which they sit. As you take the pH down, they are protonated and positively
charged. If they were in the active site, they could bind a negatively charged
group or could be involved in acid catalysis.
These are:
METHIONINE
CYSTEINE
SERINE
THREONINE
Cysteine is important as if there are two close
together in a peptide, they can form strong
covalent (disulphide bridges) between the SH
groups. This gives the protein stability. Proteins
that exist in extremely nasty environments like hot
sulphur springs can survive at 100c due to the
strong disulphide bridges that gives them tight
structures. The disulphide bond is the ONLY
covalent bond that exists in the tertiary
structure of proteins between R groups. All
the other R groups interact non-covalently.
Methionine is always found as the first amino
acid in proteins. In bacteria it is formylmethionine (it has a functional group on it that
gives it polarity). As it is aliphatic (and hence
hydrophobic) it is found buried deep inside proteins, away from water. It has a
thiol group (sulphur), protected by methylation. In some metabolic
processes, this amino acid becomes very important.
Serine and threonine have a free hydroxyl group in their side chain. They are
important in metabolic processes as that hydroxyl group is capable of
phosphorylation (being phosphorylated) it loses the H and becomes OP. This
is very important when it comes to activating enzymes for metabolic
processes. Because of this, and because they are hydrophobic, they tend to be
exposed on the outside of proteins.
Side Chains containing Nitrogen Heterocycles
These are:
PROLINE
PHENYLALANINE
TYROSINE
TRYPTOPHAN
These amino acids with aromatic side chains are
very hydrophobic. They are found on the inside
of proteins. The hydrophobic effect results in
hydrophobic amino acids such as these being
sequestered away from water it is the driving
force for protein folding.
Proline is a special amino acid it has no free
amino group. The R group makes contact
covalently with the amino group. This forms a
ring structure. This is very important in protein
structure it is called a helix breaker at the
end of a helix there is always a proline as this
stops helix formation between free amino and
carboxylate groups. The presence of an extra alkyl
group rather than a hydrogen atom on the amide
nitrogen of proline not only precludes formation of
a stabilising hydrogen bond with the usual
carbonyl group but it also introduces a steric
repulsion with that group. Proline often acts to terminate -helices and is
therefore called a helix breaker.