Revise Proteins for Cambridge 9700 (2.3)

At the heart of every protein lies the amino acid, a monomer with a distinct general structure. Each amino acid contains a central carbon atom (the alpha-carbon) bonded to four different groups: an amino group (-NH₂), a carboxyl group (-COOH), a hydrogen atom (-H), and a unique side chain known as the R-group (or variable group). It's this R-group that gives each of the 20 common amino acids its specific chemical properties (e.g., acidic, basic, polar, non-polar), which in turn influences how a protein folds and interacts.

Amino acids link together to form long chains called polypeptides. This crucial process involves a condensation reaction (also known as dehydration synthesis). The carboxyl group of one amino acid reacts with the amino group of another, releasing a molecule of water and forming a strong covalent peptide bond (-CO-NH-) between the carbon and nitrogen atoms. A molecule made of two amino acids is a dipeptide, and many linked together form a polypeptide. The reverse reaction, hydrolysis, uses water to break the peptide bond, releasing individual amino acids – a process vital during digestion.

Amino Acid₁ + Amino Acid₂ ⇌ Dipeptide + Water (Condensation/Hydrolysis)

The journey from a simple amino acid chain to a functional protein is one of intricate folding, driven by various interactions. Proteins exhibit four hierarchical levels of structure, each contributing to their final, biologically active 3D conformation.

1. Primary (1°) Structure

The primary structure is the specific sequence, number, and type of amino acids in a polypeptide chain, linked by peptide bonds. This sequence is determined by the genetic information in DNA. A change in even a single amino acid can have profound effects on the protein's final shape and function (e.g., sickle cell anaemia). 2. Secondary (2°) Structure

The polypeptide chain doesn't remain linear. It coils or folds into regular, repeating patterns. This is the secondary structure, stabilised by hydrogen bonds forming between the slightly negative oxygen of the -C=O group and the slightly positive hydrogen of the -N-H group in the polypeptide backbone (not the R-groups). The two main types are:

• α-helix: A right-handed coil, like a spring.
• β-pleated sheet: Chains lying side-by-side, linked by hydrogen bonds, forming a folded, sheet-like structure.

1. Tertiary (3°) Structure

This is the overall, complex three-dimensional folding of a single polypeptide chain. It's formed by interactions between the R-groups of the amino acids. These interactions include:

• Hydrogen bonds: Between polar R-groups.
• Ionic bonds: Between positively and negatively charged R-groups.
• Disulfide bridges: Strong covalent bonds formed between the R-groups of two cysteine amino acids.
• Hydrophobic interactions: Non-polar R-groups tend to cluster together in the protein's core, away from the aqueous environment.

1. Quaternary (4°) Structure

Some proteins consist of two or more polypeptide chains (subunits) fitted together. The way these subunits are arranged constitutes the quaternary structure. The same types of bonds that stabilise the tertiary structure also hold these subunits together. Many proteins also contain a non-protein component called a prosthetic group, which is essential for their function (e.g., the haem group in haemoglobin).

Proteins can broadly be classified into two main categories based on their overall shape and function, arising directly from their unique 3D structures:

Globular Proteins (e.g., Haemoglobin)

Globular proteins have a compact, roughly spherical shape and are generally soluble in water. This is because their hydrophobic R-groups are oriented towards the protein's core, while hydrophilic R-groups are on the surface, interacting with water. Their complex tertiary/quaternary structures create specific binding sites, making them ideal for metabolic and functional roles (e.g., enzymes, hormones, transport proteins).

Haemoglobin is a classic example. It is a transport protein found in red blood cells responsible for carrying oxygen. Its structure is:

• Quaternary: Made of four polypeptide chains (subunits) - two α-globin and two β-globin chains.
• Prosthetic Group: Each chain contains a haem group, which is a non-protein ring structure with an iron ion (Fe²⁺) at its centre. It is the Fe²⁺ that reversibly binds to one oxygen molecule (O₂).
• Function: One haemoglobin molecule can therefore carry four O₂ molecules. Its structure allows for cooperative binding, where binding one oxygen molecule increases the affinity for the next.

Fibrous Proteins (e.g., Collagen)

Fibrous proteins are formed from long, parallel polypeptide chains with little or no tertiary folding. They are insoluble in water and have a repetitive amino acid sequence, which allows them to form strong fibres or sheets. They primarily serve structural roles.

Collagen is the most abundant protein in mammals, providing high tensile strength to tissues like skin, tendons, ligaments, and bone.

• Structure: It consists of three polypeptide chains, each coiled in a helix (but not an α-helix). These three helical chains are then wound around each other to form a strong triple helix.
• Composition: It has a repetitive amino acid sequence, typically Gly-X-Y, where X is often proline. Glycine is the smallest amino acid, allowing the three chains to pack tightly together.
• Assembly: These triple helices (tropocollagen molecules) align in a staggered fashion and are cross-linked by covalent bonds to form strong collagen fibrils.