Biomacromolecules Pt IV: Proteins. Proteins Virtually everything a cell is or does depends upon the proteins it contains. Protein molecules carry out.

BiomacromoleculesPt IV: Proteins

Proteins

• Virtually everything a cell is or does depends upon the proteins it contains.

• Protein molecules carry out essential cellular functions and form the basis of many cell structures.

• Proteins show enormous functional diversity – most proteins have one specific function.

• Easiest way to recall the different functions is to remember your:

TEACHERS

TEACHERS

T is for transport proteins which carry other molecules e.g. haemoglobin

E is for enzymes which catalzye reactions e.g. ATP synthase

A is for antibodies which are involved in defence against disease

C is for contractile proteins which are involved in movement e.g. actin and myosin

H is for hormones which regulate body activity e.g. insulin

E is for exported proteins

R is for receptors which respond to stimuli e.g. insulin receptors

S is for structural proteins e.g. collagen and keratin

What are proteins?• Are macromolecules composed of linear polymers called

polypeptides.• Polypeptides are formed by condensation polymerisation of

monomers called amino acids.• Amino acids are essential biomolecules, not only because they

are the building blocks of all proteins, but because they are a source of nitrogen for many other biomolecules including nucleotides, neurotransmitters and porphyrins.

• All proteins in life forms on Earth are formed from a set of 20 amino acids.

• Most micro-organisms can synthesise the complete set of 20 amino acids, whereas humans can only make 11.

• The remaining amino acids must be supplied from the diet and are called essential amino acids.

Atoms in proteins

• Proteins contain five different types of atoms.

• This is remembered using the acronym:

SONCH

Sulfur, Oxygen, Nitrogen, Carbon, Hydrogen

Amino acids

• Amino acids have the same basic structure.

• There is an amino group (NH2), a carboxyl group (COOH) and an R group.

• The different chemical properties of individual amino acids are due to the atoms that make up the R group.

• The nature of the R side chain is important in determining the final functional shape of the protein.

• In neutral aqueous solutions such as the cell cytosol, amino acids exist in an ionized form. The acid group donates a proton (H+) to the NH2, resulting in a dipolar ion called a zwitterion.

R groups

• The R group can vary from simply one H in the case of glycine, to complex ring structures in the case of tyrosine.

• The R group contains atoms such as carbon, hydrogen, nitrogen and oxygen, and one amino acid (cysteine) contains sulphur.

• Nine amino acids have non-polar R groups (made up of hydrogen and carbon atoms) and are hydrophobic.

• The remaining eleven amino acids have polar R groups (largely due to the presence of oxygen) and are hydrophilic.

• Hydrophilic amino acids will tend to be on the surface of proteins because of their affinity with the polar water molecules in the cell environment.

• Hydrophobic amino acids will tend to be localized in the interior of the protein molecule away from water molecules.

Polypeptides• Macromolecules formed

by linking amino acid monomers to form linear unbranched chains.

• A peptide bond is formed between the amino group on one amino acid and the carboxyl group of another in a process known as condensation polymerisation.

Terminology of polypeptides

• A polypeptide chain has an unlinked amino group at one end, called the N-terminus, and an unlinked acid group at the other, called the C-terminus.

• By convention the N-terminal amino acid is depicted on the left and the C-terminal carboxyl group is on the right.

• When amino acids are linked by peptide bonds they are called amino acid residues.

• Chains of less than 20-30 residues are called peptide chains.• Chains of more than 20-30 residues are called polypeptides.• The term protein is usually reserved for a polypeptide (or complex

of polypeptides) that has a three-dimensional shape.• The size of a protein or polypeptide is reported in daltons. The

size of the average amino acid is 110 daltons.

Monomeric and multimeric proteins• A protein is a polypeptide chain or several polypeptide chains that

have achieved a unique, stable, three-dimensional structure and as a result of the final structure have biological functionality.

• Monomeric proteins

– Consist of only one polypeptide– Achieve their final shape as a result of the folding and coiling of

the polypeptide as it is formed.

• Multimeric proteins– Consist of two or more polypeptide chains– Final shape of the protein results not only from the folding and coiling

of each polypeptide but also due to the interactions between the polypeptide chains.

Haemoglobin is a multimeric protein• Haemoglobin is an

abundant protein in red blood cells that contains two copies of globin and two copies of globin.

• Each of these four polypeptide chains contains a heme molecule (red), which is the site where oxygen (O2) is bound.

• Each molecule of hemoglobin in the blood carries four molecules of oxygen.

Levels of protein structure• Primary structure• Secondary structure• Tertiary structure• Quaternary structure

Primary structure• The sequence of amino acids that make up the polypeptide. • Simply refers to the order of each amino acid from the N terminus

to the C terminus of the polypeptide. • The order of amino acids in a polypeptide is genetically

determined.• Three amino acids of importance structurally are:

– Cysteine: R side chain contains a sulfur atom that can bond with another sulfur molecule in an adjacent molecule to form a disulfide bond.

– Proline: R side chain is a cyclic ring. This makes it very rigid and results in a fixed kink in a polypeptide chain.

– Glycine: R side chain is a single H atom making glycine the smallest amino acid, and therefore able to fit into tight spaces.

Secondary structure

• Different parts of a polypeptide assume different geometric arrangements due to interactions between amino acid residues.

• These interactions stabilise the backbone of the polypeptide producing three types of secondary structure: – alpha helix– beta sheet– random coils

• Secondary structure is a predictable repeating pattern, due to hydrogen bonding between peptide bonds.

Secondary structure• Alpha helix

– coils formed due to H bonds between =O on one amino acid residue and the amide H on the next amino acid

• Beta sheet– Folds perpendicular to the plane of the

sheet. – Stabilised by H bonds. – May be intramolecular or intermolecular.

• Random coils– Any portion of a polypeptide that does not

show alpha helices or beta sheets is termed a random coil.

– Random coils are commonly found making up the active sites of enzymes.

Tertiary structure• Folding of the polypeptide chain that results in a

stabilised overall three-dimensional shape called the conformation.

• Depends upon the R-group of each amino acid residue.• Final shape is determined by competing

interactions between the R groups, each with different properties.– Covalent bonds form between sulfur

molecules in adjacent cysteine residues.– Hydrophobic R groups will associate

together and seek out a non-aqueous environment.

– Hydrophilic R groups will associate together and be drawn to an aqueous environment.

More about tertiary structure• Proteins can be divided into two broad groups based on their tertiary

structure: fibrous proteins and globular proteins.

• Fibrous proteins– Have extensive alpha helixes or beta sheets, giving them a highly ordered

repetitive structure. – In these proteins the secondary structure is more important than the

tertiary structure as they have an extended filamentous structure. – Examples of fibrous proteins are fibroin (silk) and keratins (hair, wool) as well

as collagen (in skin) and elastin (ligaments and blood vessels).

• Globular proteins– Have polypeptides folded into compact shapes rather than extended filaments. – Within the compact shape are regions of alpha helixes and regions of beta

sheets interspersed with random coils, – These irregular structured regions allow the polypeptide chain to loop

and fold thus giving the protein its functional shape or conformation. – Most proteins involved in cellular functions are globular proteins e.g.

haemoglobin.

Quaternary structure

• Is only present in a protein if it is made up of more than one polypeptide chain.

LEVEL OF ORGANISATION

STRUCTURAL FEATURES

TYPES OF BONDS AND INTERMOLECULAR

INTERACTIONS

PrimaryLinear sequence of amino acids.

Covalent peptide bond linking amino acid residues.

Secondary

Coiling into helices and folding into sheets in parts of the polypeptide chain. Non-folded regions are called random coils.

Hydrogen bonding.

Tertiary

Folding of the polypeptide resulting in a 3D shape that is stabilised by various intermolecular interactions.

Hydrogen bonds.

Ionic bonds.

Van der Waals interactions.

Hydrophobic interactions.

Disulfide bonds.

Quaternary

Association of two or more folded polypeptides to form a protein.

Ionic bonds.

Van der Waals interactions.

Hydrophobic interactions.

Disulfide bonds.