Proteins II and III

Protein Structure: Secondary, Tertiary, and Quaternary

Proteins exhibit hierarchical structural organization, each level stabilized by distinct interactions and forces.

• Secondary Structure: Local folding patterns such as α-helices and β-sheets, stabilized by hydrogen bonds between backbone amide and carbonyl groups.

• Tertiary Structure: Overall 3D folding of a single polypeptide chain, stabilized by hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bridges.

• Quaternary Structure: Assembly of multiple polypeptide subunits, stabilized by non-covalent interactions and sometimes covalent bonds.

• Thermodynamic Forces: Protein folding is driven by the hydrophobic effect, enthalpic and entropic contributions, and minimization of free energy ().

• Examples: Hemoglobin (quaternary), Myoglobin (tertiary).

Protein Motifs and Domains

Motifs and domains are recurring structural elements in proteins, each with specific functions.

• Motif: Short, conserved sequence or structural element (e.g., helix-turn-helix, zinc finger).

• Domain: Independently folding region of a protein, often associated with a specific function (e.g., SH2 domain).

• Examples: Immunoglobulin domain, leucine zipper motif.

Physicochemical Properties of Proteins

Proteins possess unique chemical and physical properties that influence their function and stability.

• Solubility: Depends on amino acid composition and pH.

• Isoelectric Point (): The pH at which a protein carries no net charge.

• Hydrophobicity: Influences folding and membrane association.

Protein Folding and Denaturation

Protein folding is a highly regulated process, while denaturation disrupts native structure.

• Folding: Achieves native conformation via chaperones and folding pathways.

• Denaturation: Loss of structure due to heat, pH, chemicals; often reversible.

• Equation:

Post-Translational Modifications (PTMs)

PTMs diversify protein function and regulation.

• Types: Phosphorylation, glycosylation, acetylation, methylation, ubiquitination, disulfide bond formation.

• Example: Phosphorylation of serine residues in enzymes.

Protein Purification and Visualization

Proteins are isolated and analyzed using various biochemical techniques.

• Purification: Chromatography (ion exchange, size exclusion, affinity), electrophoresis.

• Visualization: SDS-PAGE, Western blotting, staining (Coomassie, silver).

• Structure Determination: X-ray crystallography, NMR spectroscopy, cryo-EM.

Carbohydrates and Glycoproteins

Stereochemistry: Enantiomers, Diastereoisomers, Epimers, Anomers

Carbohydrates exhibit complex stereochemistry, crucial for their biological roles.

• Enantiomers (D, L): Mirror images differing at all chiral centers; D/L designation based on the configuration at the penultimate carbon in Fischer projections.

• Diastereoisomers: Stereoisomers not related as mirror images; differ at one or more (but not all) chiral centers.

• Epimers: Diastereoisomers differing at only one chiral center.

• Anomers: Isomers differing at the anomeric carbon (α or β) in cyclic forms.

Glycosidic Bonds in Haworth Projections

Glycosidic bonds link monosaccharides in oligo- and polysaccharides.

• Notation: α-1,4 (linear), α-1,6 (branching in glycogen).

• Identification: Recognize bond type and position in Haworth projections.

Reducing and Non-Reducing Sugars

Disaccharides can be classified based on their ability to reduce oxidizing agents.

• Reducing Sugar: Has a free anomeric carbon capable of acting as a reducing agent.

• Non-Reducing End: Anomeric carbon involved in glycosidic bond.

• Example: Maltose (reducing), sucrose (non-reducing).

Solubility of Polysaccharides

Structural differences dictate water solubility of polysaccharides.

• Glycogen: Highly branched, water soluble.

• Cellulose and Chitin: Linear, extensive hydrogen bonding, insoluble.

Glycosaminoglycans (GAGs)

GAGs are long, unbranched polysaccharides with repeating disaccharide units.

• Structure: Alternating amino sugars and uronic acids.

• Example: Hyaluronan, chondroitin sulfate.

Proteoglycans and Glycoproteins

These macromolecules are essential for cell-cell recognition and extracellular matrix function.

• Proteoglycans: Core protein with covalently attached GAGs; structural and signaling roles.

• Glycoproteins: Proteins with oligosaccharide chains; involved in recognition, immunity.

Lipids

Functions and Classes of Lipids

Lipids serve diverse biological functions and are classified by structure.

• Functions: Energy storage, membrane structure, signaling.

• Classes: Fatty acids, triacylglycerols, phospholipids, steroids, terpenes, prostaglandins.

Structures of Major Lipids

Understanding lipid structure is key to their function.

• Fatty Acid: Long hydrocarbon chain with terminal carboxyl group.

• Triacylglycerol: Glycerol backbone esterified with three fatty acids.

• Phospholipid: Glycerol backbone, two fatty acids, phosphate group with head group.

• Cholesterol: Four fused hydrocarbon rings with hydroxyl group.

Lipoproteins

Lipoproteins transport lipids in the bloodstream.

• Structure: Core of triglycerides and cholesterol esters, surrounded by phospholipids and apolipoproteins.

• Function: Transport and metabolism of lipids (e.g., LDL, HDL).

Types of Phospholipids

Phospholipids vary by head group and fatty acid composition.

• Types: Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin.

• Identification: Recognize by molecular structure.

Cholesterol: Structure and Function

Cholesterol is a key membrane component and steroid precursor.

• Structural Role: Modulates membrane fluidity and stability.

• Precursor: Steroid hormones, bile acids, vitamin D.

Terpenes

Terpenes are a diverse class of lipids derived from isoprene units.

• Types: Monoterpenes, diterpenes, triterpenes, etc.

• Example: Squalene (triterpene), limonene (monoterpene).

Prostaglandins

Prostaglandins are lipid-derived signaling molecules.

• Function: Mediate inflammation, pain, fever, and other physiological processes.

• Structure: Derived from arachidonic acid; contain a five-membered ring.

Membranes and Transport

Biological Membranes: Structure and Dynamics

Membranes are dynamic assemblies of lipids and proteins, essential for cellular compartmentalization.

• Organization: Lipid bilayer with embedded proteins.

• Dynamics: Lateral diffusion, fluid mosaic model.

Role of Phospholipids, Cholesterol, and Proteins

Membrane composition determines its properties and functions.

• Phospholipids: Form bilayer, provide barrier.

• Cholesterol: Modulates fluidity and permeability.

• Proteins: Transport, signaling, structural support.

Membrane Adaptations and Asymmetry

Membranes exhibit structural adaptations and compositional asymmetry.

• Adaptations: Varying lipid composition for temperature adaptation.

• Asymmetry: Different lipid and protein distribution between leaflets.

Membrane Proteins: Types and Insertion

Membrane proteins are classified by their association with the bilayer.

• Types: Integral, peripheral, lipid-anchored.

• Insertion: Transmembrane domains, post-translational modifications.

Membrane Transport Mechanisms

Transport across membranes occurs via several mechanisms, each with distinct biochemical principles.

• Passive Transport: Simple diffusion, facilitated diffusion (channels, carriers).

• Active Transport: Requires energy (ATP), e.g., Na+/K+ pump.

• Equation: (Fick's law for passive diffusion)

• Example: Glucose transport via GLUT proteins.