Protein Structures: Secondary to Quaternary

Secondary, Tertiary, and Quaternary Protein Structures

• Proteins have four levels of structure.
• The primary structure is the sequence of amino acids.
• Secondary structure involves hydrogen bonding between amino acids, creating patterns like alpha helices and beta pleated sheets.
• Tertiary structure is the three-dimensional folding pattern of a protein.
• Quaternary structure is the arrangement of multiple polypeptide chains in a protein.

Learning Outcomes

• Understanding different structural shapes of proteins is essential.
• Different types of bonding and interactions hold proteins in their 3D shapes.
• Examples of secondary and tertiary structures are crucial.
• How protein shape changes can contribute to diseases must be understood.

Primary Structure of Proteins

• The primary structure is the sequence of amino acids in a polypeptide chain.
• A main backbone and distinctive side chains are present.
• Peptide bonds hold amino acids together.
• Polypeptides range from 50–300 amino acids, with Titin containing 27,000.
• Each amino acid is a "residue" or "moiety."
• Structure runs from the amino (N) terminus to the carboxyl (C) terminus.

What is a Protein?

• Proteins are chains of amino acids joined by peptide bonds.
• Proteins fold into compact 3D shapes (conformational).
• 3D shapes have been determined for 50 years now
• Changes in protein shape are possible without breaking bonds under normal conditions, leading to a stable state (native form).
• Biological function depends on the 3D shape.

Folding

• Protein folding creates three-dimensional structures.
• Secondary structure includes elements like alpha helices and beta pleated sheets.
• Tertiary structure results from interactions between side chains.
• Quaternary structure involves the combination of multiple polypeptide chains.
• Non-covalent interactions (hydrogen bonds and disulfide bonds) drive folding.

Secondary Protein Structure

• Secondary structure results from hydrogen bonds between the polypeptide backbone's amino and carboxyl groups.
• Regular intervals along the backbone form these bonds.
• Two main secondary structures are alpha helices and beta pleated sheets.

Alpha Helix

• Coiled structure with hydrogen bonds between amino acids spaced every four residues.
• R-groups point outwards and are not involved in hydrogen bonding directly.
• Proline is often a helix-breaker do to it's lack of a hydrogen.

Beta Sheets

• "Pleated" sheets formed by hydrogen bonds between polypeptide chains.
• Hydrogen bonds are formed between the carbonyl oxygens and amide hydrogen groups of adjacent segments.
• Can be parallel or anti-parallel arranged, with anti-parallel structures more stable.

Secondary Structures (Other)

• Structures of non-repeating 3D structures are considered secondary structures.
• Characterised as turns or loops.
• Changes occur in the polypeptide backbone and connect alpha- and beta-strands.
• Loops often contain hydrophobic amino acids.
• Turns contain four to five residues.
• Beta turns are a common way segments change directions.

Motifs

• Super-secondary structures are combinations of alpha helices, beta strands, and loops in proteins.
• Specific combinations associated with particular functions (e.g., helix-loop-helix, zinc-finger, leucine zipper motifs)
• Structural motifs show repeated patterns within and between proteins, and function is often associated with these motifs.

Fibrous Proteins

• Structural support proteins.
• Tough and insoluble in water.
• Examples include alpha-keratin, collagen, and silk fibroin.

Alpha Keratin

• Composed of two right-handed alpha helices wrapped into a left-handed superhelix.
• Coiled-coil motif rich in hydrophobic amino acids (Ala, Val, Leu, Ile, Met, Phe).
• Very strong structural protein.

Disulfide Bonds and Hair Styling

• Ammonium thioglycolate cleaves disulfide bonds in hair.
• Chemical hair treatments use oxidizing agents to reform disulfide bonds.
• These bonds affect hair's shape and stability.

Silk Fibroin

• Produced by silkworms and spiders.
• Composed of antiparallel beta pleated sheets, which are rich in alanine and glycine.
• Inflexible but flexible due to interactions.

Collagen

• Most abundant protein in mammals.
• Unique secondary structure of three helical polypeptide chains forming a coiled coil.
• Glycine appears every third residue, adding to its strength.

Chilean Blob Mystery

• A significant blob found on a beach in Chile was investigated.
• The blob was found to consist of tough, collagen fibers resistant to degradation.
• Genetic analysis identified the blob as a sperm whale.

Tertiary Protein Structure

• Polypeptide chains are completely folded and compacted into a 3D structure.
• Made up of several distinct globular units linked by short stretches of amino acids.
• Individual units termed domains.
• Motifs are combinations of secondary structures forming larger tertiary motifs.
• Interactions of amino acid side chains stabilize the folding.

Residues

• Polypeptide chains may be extensive and may have exposed regions referred to as residues.
• Residues can have unique functions.
• Hydrophobic and hydrophilic residues often play roles as protection and function.

G Protein-Coupled Receptors

• Largest receptor family in mammals.
• Single 400–500 polypeptide chains, traversing the membrane seven times.
• Common drug targets for various diseases.

Protein Folding And Stability

• Rapid chain reactions to form a native conformation via non-covalent forces.
• These forces include hydrophobic effects, hydrogen bonding, and van der Waals interactions.
• Weak forces contribute to overall stability.

Hydrophobic Effect

• Proteins are more stable in water when hydrophobic side chains are aggregated inside.
• This minimizes contact with water.
• Side chains interact to force the polypeptide chain to collapse and form a more compact structure.

Van der Waals and Charge–Charge Interactions

• These interactions (non-covalent) affect protein stability.
• Van der Waals forces occur among nonpolar amino acid side chains.
• Charge–charge interactions involve oppositely charged amino acid side chains.

Myoglobin – Structure

• Globular protein.
• Polypeptide chain containing 153 amino acids.
• Eight alpha helices stabilized by hydrogen bonding.
• Oxygen-binding protein with a compact structure.
• Interior is predominantly nonpolar amino acids.

Myoglobin – Amino Acid Distribution

• Protein folding driven by the hydrophobic effect.
• Hydrophobic amino acids cluster in the interior of the protein.
• Charged amino acids, hydrophilic, are located on the outside of the protein.

Quaternary Protein Structures

• Some proteins consist of two or more polypeptide chains (also called subunits) forming a multi-subunit protein.
• Subunits assembled to give the quaternary structure.
• Chaperones assist the process of assembling these structures.
• The polypeptide chains can be identical or different, such as in the haemoglobin protein.

Protein Denaturation

• A change in the protein's 3D shape (conformation).
• The native state (unfolded state) loses its shape.
• The shape change is due to disruptions in disulfide bonds, hydrogen bonds, and other non-covalent interactions.
• Causes may include heat or strong chemicals.
• Protein can lose function if denatured.

Disruption of Neuronal Action in Alzheimer's Disease

• Amyloid plaques and neurofibrillary tangles disrupt brain function.
• The process results from abnormalities in the cleavage of precursor protein.
• Loss of neuronal function can lead to Alzheimer's.