Protein Structures Quiz

Protein Structure and Function

Primary Structure

• A peptide is comprised of at least three amino acids linked by two peptide bonds
• Amino acids in proteins are called residues
• The bonds either side of the α-carbon can rotate and are defined by phi (φ) and psi (ψ) angles
• The peptide bond has partial double-bond like character and is stabilized by electron resonance

Secondary Structure

• Regular arrangements of the backbone of amino acids located next to each other in 3D space
• Examples: α-helices, β-sheets, and turns
• α-helices have 3.6 amino acids per turn and are stabilized by hydrogen bonds between backbone amide (N-H) and carbonyl (C=O) groups

Tertiary Structure

• The final 3D structure of a protein
• Determined by the interactions between side chains (R groups) and the backbone
• Can be unfolded, or denatured, by various conditions (e.g. high temperature, pH, detergents or solvents)

Quaternary Structure

• The arrangement of multiple polypeptide chains (subunits) in a protein
• Subunits interact and 'bind' mainly through non-covalent interactions
• Examples: haemoglobin has four subunits and is the active structure, insulin is stored in a complex of six subunits but the monomer is the active structure

Protein Folding and Misfolding

• The linear protein chain spontaneously folds into its final 3D structure
• Misfolded proteins can accumulate, particularly as individuals age, and lead to diseases such as amyloidoses (e.g. Alzheimer's disease) and prion diseases

Protein Function and Importance

• Proteins perform most of the functions in the cell
• They comprise most of the dry mass of a cell, an indication of their importance
• They are highly specific and act through 3D stereospecific interactions
• They have diverse functions, including catalysis, transport, storage, motion, structural support, immunity, and growth and development

Visualising Protein Structure

• Experimental data: X-ray diffraction (XRD) crystallography, nuclear magnetic resonance (NMR) spectroscopy, molecular models
• Molecular visualisation programs: Swiss-PDBViewer, VMD, Pymol

Mutations and Disease

• A single amino acid change can lead to disease, e.g. sickle cell haemoglobin

• Mutations in collagen (insoluble fibrous protein) or collagen-processing enzymes can lead to diseases such as osteogenesis imperfecta and Ehlers-Danlos syndrome### Protein Structure

• A peptide is comprised of at least three amino acids linked by two peptide bonds.

• Amino acids in proteins are called residues.

• Peptide bonds have partial double-bond like character, are stabilized by electron resonance, and are shorter than a single bond.

• The peptide bond is rigid and planar, polar, and can form hydrogen bonds.

Primary Structure

• The primary structure of a protein is the linear sequence of amino acids.
• The bonds either side of the α-carbon can rotate and are defined by phi (φ) and psi (ψ) angles.
• The peptide/protein chain backbone can thus bend or fold to form compact structures.

R Groups

• R groups in peptides most often alternate on either side of the backbone.
• Peptide bonds are usually in a trans configuration due to steric constraints.
• Cis configuration can occur with proline due to the cyclic nature of its side chain.

Secondary Structure

• Regular arrangements of the backbone of amino acids located next to each other in 3D space.
• Internal protein structures and patterns can be seen in molecular representations of proteins.

α-Helix

• Each helical turn has 3.6 amino acids.
• Hydrogen bonds stabilize the structure between backbone amide (N-H) and carbonyl (C=O).
• Occur between residue n and residue n+4 in the chain.

Visualizing Proteins

• Various styles of visualizing proteins include stick, ball and stick, space-fill, opaque, plastic, metal, and cartoon/ribbon representations.

Importance of Proteins

• Proteins are amazing molecular machines with great diversity.
• The constellation of all proteins in a cell is called its proteome.
• Unravelling the proteome is the current challenge!

Protein Function

• Protein structure and function determines protein sequence determines protein structure.
• Secondary, supersecondary, domain, tertiary, and quaternary structures determine protein function.
• Biological functions of proteins include catalysis, transport, storage, motion, structural support, immunity, and many others.