3.4 Proteins

Proteins are the most functionally diverse molecules in your cells. They catalyze reactions, provide structural support, transport materials, and send signals. That versatility comes down to one thing: their shape. And their shape comes from how amino acids link together and fold.

Protein Structure and Function

Functions of proteins

Proteins take on a huge variety of roles depending on their structure. Here are the major categories you need to know:

• Enzymes catalyze biochemical reactions by lowering activation energy, which speeds up reaction rates. Without enzymes, most cellular reactions would be far too slow to sustain life.
• Structural proteins provide support and shape to cells and tissues. Collagen strengthens connective tissue, keratin toughens skin and hair, and elastin gives tissues their ability to stretch and snap back.
• Transport proteins move molecules across cell membranes or through the body. Hemoglobin carries oxygen in red blood cells, while channel proteins allow specific ions to pass through membranes.
• Signaling proteins facilitate communication between cells. Hormones like insulin travel through the bloodstream to deliver messages, while receptors on cell surfaces detect those signals.
• Antibodies recognize and bind to specific foreign substances (antigens), helping the immune system target infections.
• Contractile proteins enable movement. Actin and myosin interact inside muscle cells to drive contraction.

Amino acids as protein components

Amino acids are the monomers (building blocks) of proteins. There are 20 different amino acids commonly found in proteins, and the specific sequence in which they're arranged determines what the protein becomes.

Every amino acid shares the same core structure:

• A central carbon atom (the α-carbon)
• An amino group ($-NH_2$)
• A carboxyl group ($-COOH$)
• A hydrogen atom
• A unique R group (side chain)

The R group is what makes each amino acid different. Some R groups are nonpolar and hydrophobic, others are polar or electrically charged. These chemical properties drive how the protein folds later on.

Peptide bond formation: When two amino acids join, the carboxyl group of one reacts with the amino group of the next in a condensation (dehydration synthesis) reaction, releasing a water molecule. The covalent bond that forms between them is called a peptide bond. A chain of amino acids linked by peptide bonds is called a polypeptide.

Levels of protein structure

Proteins have up to four levels of structure, each building on the one before it:

1. Primary structure is the linear sequence of amino acids in the polypeptide chain. This sequence is determined by the gene that encodes the protein. Even a single amino acid change can alter function (sickle cell disease results from just one amino acid substitution in hemoglobin).

2. Secondary structure refers to local folding patterns within the chain, driven by hydrogen bonds between the backbone atoms (not the R groups). The two main types are:

   • α-helices: coiled, spring-like structures
   • β-pleated sheets: flat arrangements where strands line up side by side (parallel or antiparallel) and are connected by hydrogen bonds between strands Most proteins contain a mix of both.

3. Tertiary structure is the overall 3D shape of a single polypeptide chain. This level is stabilized by interactions between R groups, including:

   • Hydrogen bonds
   • Ionic bonds
   • Hydrophobic interactions (nonpolar R groups cluster away from water)
   • Disulfide bridges (covalent bonds between sulfur atoms in cysteine residues) Tertiary structure is what gives a protein its specific shape and, therefore, its function. Chaperone proteins assist in proper folding, helping polypeptides reach their correct 3D conformation.

4. Quaternary structure exists only in proteins made of two or more polypeptide chains (subunits). These subunits are held together by the same types of interactions found in tertiary structure. Hemoglobin is a classic example: it consists of four polypeptide subunits working together to carry oxygen.

Protein shape and function relationship

A protein's shape is directly tied to its function. If the shape changes, function is usually lost or altered.

• Active sites on enzymes have a shape and charge that are complementary to their substrate. This specificity is why each enzyme typically catalyzes only one reaction.
• Binding sites allow proteins to interact with specific molecules like hormones or drugs. The fit depends on shape and charge, much like a lock and key.
• Conformational changes are shifts in a protein's shape, often triggered by ligand binding or changes in the environment. These shape changes can activate or deactivate the protein. Allosteric regulation is a specific type where a molecule binds at a site other than the active site, causing a shape change that affects activity.

Denaturation occurs when a protein loses its 3D structure due to extreme heat, pH changes, or exposure to certain chemicals. The peptide bonds (primary structure) remain intact, but the higher-level folding unravels, and the protein can no longer function.

Misfolded proteins are a serious problem. When proteins fold incorrectly, they can clump together into aggregates. This is linked to diseases like Alzheimer's (amyloid plaques) and Parkinson's (Lewy bodies).

Protein Regulation and Interactions

Once proteins are made, cells still have ways to control and modify them.

• Post-translational modifications are chemical changes made to a protein after it's synthesized. Adding phosphate groups, sugars, or lipids can change a protein's activity, location, or stability.
• Proteases are enzymes that break peptide bonds, degrading proteins. This is important for recycling amino acids and for regulating how long a protein stays active in the cell.
• Protein-protein interactions are specific physical contacts between two or more proteins. Many cellular processes, from signaling pathways to DNA replication, depend on proteins binding to each other in precise ways.
• Proteomics is the large-scale study of all the proteins in a cell or organism, including their structures, functions, and interactions. It goes beyond studying one protein at a time to look at the full picture.