Introduction to Proteins and Amino Acids

• Proteins are essential macromolecules for all known life forms
• Proteins are amino acid polymers, connected by peptide bonds.
• Proteins catalyze reactions, replicate DNA, respond to stimuli, provide structure, and transport molecules.
• The amino acid sequence, determined by genes, dictates a protein's unique 3D structure and activity.

Amino Acids

• Amino acids have an amino and a carboxyl group.
• Amino acids are protein building blocks.
• L-amino acids are linked by peptide bonds in polypeptide chains in proteins.
• There are 20 common amino acids in proteins.
• Each amino acid has a unique side chain (R group) determining its properties.
• Amino acids are classified by side chain properties: polar, nonpolar, acidic, or basic.
• Amino acids are chiral, except glycine.
• Amino acids are amphoteric, having acidic and basic groups.
• At physiological pH, they exist as zwitterions with positive and negative charges.
• The isoelectric point (pI) is the pH where an amino acid has no net charge.

Polypeptide Formation

• Proteins consist of amino acids linked by peptide bonds.
• A peptide bond is a covalent bond between the carboxyl group of one amino acid and the amino group of another.
• Peptide bond formation involves dehydration.
• Polypeptides have directionality (N-terminal and C-terminal ends).
• The amino acid sequence is a protein's primary structure.
• Polypeptides vary in length.
• Amino acid composition and sequence determine polypeptide properties.

Protein Structure

• Protein structure has four levels: primary, secondary, tertiary, and quaternary.

Primary Structure

• Primary structure is the linear sequence of amino acids.
• The primary structure dictates higher-level structures and protein function.
• Peptide bonds formed during biosynthesis hold the primary structure together.
• Amino acid sequence is unique and genetically encoded.
• Edman degradation or mass spectrometry can experimentally determine primary structure.

Secondary Structure

• Secondary structure involves local, regular structures with hydrogen bonds in the peptide backbone.
• Alpha-helices, beta-sheets, and turns are common secondary structures.
• Alpha-helices are coiled, stabilized by hydrogen bonds between carbonyl oxygen and amide hydrogen four residues down the chain.
• Beta-sheets are formed by hydrogen bonds between polypeptide strands, either parallel or antiparallel.
• Turns are short, U-shaped structures connecting secondary structure elements.
• Amino acid sequence influences secondary structure elements.

Tertiary Structure

• Tertiary structure is the overall 3D shape of a single polypeptide chain.
• Hydrophobic interactions, hydrogen bonds, ionic bonds, and disulfide bridges stabilize it.
• Hydrophobic interactions occur between nonpolar side chains in the protein's interior.
• Hydrogen bonds form between polar side chains and the peptide backbone.
• Ionic bonds form between oppositely charged side chains.
• Disulfide bridges are covalent bonds between cysteine residues.
• Tertiary structure is crucial for protein function, shaping the active site and allowing interaction with other molecules.

Quaternary Structure

• Quaternary structure is the arrangement of multiple polypeptide chains (subunits) in a multi-subunit protein.
• Not all proteins have it; only those with multiple polypeptide chains do.
• Subunits are held together by non-covalent interactions.
• Proteins with quaternary structure can be dimers, trimers, tetramers, or larger complexes.
• Quaternary structure affects protein stability, allosteric regulation, and interactions.

Protein Folding

• Protein folding allows a polypeptide chain to attain its native 3D structure.
• It is driven by the amino acid sequence and influenced by factors like temperature and pH.
• The process includes forming secondary structures, polypeptide chain collapse, and rearrangement to achieve the native conformation.
• Chaperone proteins prevent aggregation and misfolding, assisting in protein folding.
• Misfolded proteins form toxic aggregates, causing diseases like Alzheimer's and Parkinson's.
• Diseases from misfolded proteins are called protein misfolding or aggregation diseases.

Protein Function

• Proteins catalyze, transport, store, move, provide structural support, defend, and regulate.

Enzymes

• Enzymes are proteins that catalyze biochemical reactions, increasing reaction rates.
• Enzymes are specific to their substrates, increasing reaction rates significantly.
• Enzymes have an active site for substrate binding and reaction.
• Enzyme activity is regulated by temperature, pH, inhibitors, or activators.

Transport Proteins

• Transport proteins bind and carry specific molecules.
• Examples are hemoglobin (oxygen transport) and membrane transporters.

Storage Proteins

• Storage proteins store essential substances.
• Ferritin (iron storage) and casein (milk protein) are examples.

Motor Proteins

• Motor proteins convert chemical energy (ATP) into mechanical work to generate movement.
• Myosin (muscle contraction) and kinesin (intracellular transport) are examples.

Structural Proteins

• Structural proteins provide cell and tissue support.
• Collagen (connective tissue) and keratin (hair, skin, nails) are examples.

Defense Proteins

• Defense proteins protect against disease.
• Antibodies and blood clotting factors are examples.

Regulatory Proteins

• Regulatory proteins control cellular functions.
• Transcription factors and hormones are examples.

Protein Modification

• After synthesis, proteins undergo post-translational modifications (PTMs) affecting structure and function.
• Common PTMs: phosphorylation, glycosylation, ubiquitination, and acetylation.
• Phosphorylation adds a phosphate group to serine, threonine, or tyrosine.
• Glycosylation adds a sugar molecule to asparagine or serine.
• Ubiquitination adds ubiquitin to lysine.
• Acetylation adds an acetyl group to lysine.
• PTMs impact protein folding, stability, interactions, and activity.

Protein Degradation

• Protein degradation breaks down proteins into amino acids.
• It removes damaged proteins and regulates protein levels.
• The ubiquitin-proteasome system and autophagy are major pathways.
• The ubiquitin-proteasome system tags proteins with ubiquitin for proteasome degradation.
• Autophagy engulfs proteins in autophagosomes, which fuse with lysosomes for degradation.