Special topics Lecture 2

Protein structure

Primary structure

Protein sequence (primary structure) is determined by DNA sequence, peptide bonds are covalent bonds between a sequence of amino acids residues (relatively strong), the polypeptide starts to form secondary structures as it leaves the ribosome, N-terminus to C-terminus

Secondary structure

Held by weak but many hydrogen bonds to form alpha helix and beta sheets, determined by the specific sequence of amino acids from the primary structure

Tertiary structure

Polypeptide chain folds further to form a 3D shape stabilised by side chain interactions and is determined by the specific sequence of amino acids from the primary structure, hydrophobic amino acids clusters in the middle while the hydrophilic ones are on the surface.

Quaternary structure

Two or more polypeptide chains associate together to form a larger functional protein, not all proteins form quaternary structures

Amino acid structure

Amino (base) group, side chain, carboxyl (acid) group, and an alpha carbon.

Polypeptides

Polypeptides are a sequence of amino acids that are joined together by a peptide bond via a dehydration reaction

It can also be reversed via a hydrolysis reaction

Alpha helix

When the backbone forms spiral shape which has 3 - 4 amino acids per turn with the side chains pointing out of the helix

Beta sheets

Occurs when the backbone extends one way and turns back to line up parallel to the initial sheet

The hydrophobic effect

The tendency of 3D protein structures to create a hydrophobic middle and a hydrophilic surface

Globular proteins

3D proteins that are highly folded and compact

Fibrous proteins

3D proteins that are long and spindly

Cysteine

An amino acid containing a thiol group, important for forming disulfide bonds in proteins, stabilizing their 3D structure.

Tetramer

A quarternary protein structure that is comprised of 4 individual polypeptide chains coming together

Dimers

A quaternary protein structure formed by 2 polypeptide chains that are bound together.

Dimer of dimers

A quaternary protein structure consisting of 2 dimers (each formed by 2 polypeptide chains) that associate to create a larger complex.

Forces maintaining protein structures

Multiple weak interactions such as hydrogen bonding, electrostatic interactions, disulphide bonds and hydrophobic interactions

Hydrogen bonds

Plays a crucial role in protein folding, forming backbone hydrogen bonds in secondary and tertiary protein structures, stabilising it, and be involved in the active site of enzymes

Electrostatic interactions

Ionic interactions or salt bridges that occur between charged side chains of amino acids, stabilizing protein structure.

Disulphide bonds

Can occur spontaneously under mild oxidation conditions and when two cysteines come close together

Hydrophobic interactions

Hydrophobic side chains come together to form a hydrophobic core away from water, weakest type of interaction but has strength in numbers that drives protein folding in the tertiary structure

Causes of denaturation

Change in pH, salt concentration, temperature

Denaturation

A permanent change in structure or chemistry of the protein which changes its function due to the hydrophobic effect not being able to occur

Structural guided drug discovery

A method that utilizes the three-dimensional structure of biomolecules to design and optimize potential drug candidates, enhancing specificity and efficacy.

X-ray crystallography

A technique used to determine the atomic and molecular structure of a crystal/protein by diffracting X-ray beams through it.

Cryo-electron microscopy

A technique that allows for the visualization of protein structures at very low temperatures, producing high-resolution images of complexes like proteins and viruses.

NMR

Nuclear magnetic resonance uses magnetic fields and radio waves to determine the structure and dynamics of molecules, particularly proteins and nucleic acids, in solution.