Biochemistry Protein Structure Quiz

Lecture 3: Proteins

• The lecture was presented by Randa A. Zaghloul, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
• The course is Biochemistry-1.

Recap

• The lecture covered the following topics: What is Biochemistry 1 about, carbohydrates, proteins, and amino acids.

Learning Objectives

• The objectives were to learn about the level of folding of proteins and post-translational modification.

Classification of Amino Acids

• Nutritional value: Glycine, Alanine
• Biological value: Valine, leucine, isoleucine, threonine, serine, cysteine, methionine, proline
• Polarity of side chains: Phenylalanine, tyrosine, tryptophan, arginine, lysine, histidine, glutamate, aspartate, glutamine, asparagine

Biologically Active Oligopeptides:

• Glutathione : A tripeptide (γ-Glutamyl-cysteinyl glycine), functions as an antioxidant.
• Oxytocin and Vasopressin: Nona peptides secreted by the posterior lobe of the pituitary gland.
  • Oxytocin: Uterine contraction, induction of labor.
  • Vasopressin (ADH): Peripheral blood vessel constriction, increases blood pressure.

Levels of Protein Structure

• Figure 2: Illustrates the primary, secondary, tertiary, and quaternary levels of protein structure visually.

Hierarchical Structure of Proteins

• Protein chains fold into unique shapes stabilized by non-covalent interactions.
• The 3D shape is crucial for function.
• Protein structure is complex, involving four organizational levels.

Primary Structure

• Definition: The sequence of amino acids in a protein.
• Importance: Many genetic diseases are caused by abnormal amino acid sequences, affecting protein folding and function.
• Bonds: Amino acids are joined covalently by peptide bonds.
• Molecular Weight: Protein size is reported as mass in daltons or molecular weight (MW).

Secondary Structure

• Definition: Regularly repeating structures.
• Importance: Without secondary structure, proteins would form long, spaghetti-like molecules. Secondary coils and folds are formed due to H-bonds between backbone constituents.
• Bonds: H- bonds.
• Types: α-helix, β-pleated sheet, β-turns.

Protein Structure

• α-helix: Rod-like structure; side chains extend outward from the central axis; hydrogen bonds stabilize the helical structure.
• β-pleated sheets: Polypeptide chains line up side-by-side to from sheets; stabilized by hydrogen bonds; found in globular proteins and often form a core.

Tertiary Structure

• Definition: The overall 3D shape of the entire protein molecule.
• Importance: Formation and arrangement of domains within the protein.
• Bonds: Interactions between R groups, rather than backbone constituents.

Hydrophobic interactions, covalent cross-linkages:

• Non-polar side chains fold to protein interior; polar/charged side chains tend to be on the surface of the molecule.
• Disulphide bonds are covalent bonds between the (-SH) of two cysteine residues; formation of cystine; may be separated by many amino acids in the primary structure; may be on different polypeptide chains.

Types of proteins

• Globular proteins: Roughly spherical shape, varying coils with no regular structure.
• Fibrous proteins: Straight chain, with a regular structure. In tissues like hair and skin.

Domain

• Functional and 3D structural units.
• Polypeptide chains > 200 amino acids consist of two or more domains.

Quaternary Structure

• Formed from multiple polypeptide chains (subunits).
• Subunits can be the same or different.
• Interactions between subunits form larger aggregates.
• Stabilized by H-bonds, disulfide bridges, and salt bridges.
• Examples: Collagen (three coiled polypeptides) and Hemoglobin (four polypeptides: two alpha and two beta).

Post-translational Modifications

• Modifications occur after protein synthesis on ribosomes; altering function, lifespan, and location.
• Examples:
  • Acetylation: Adding an acetyl group to the N-terminal residue (common and influences lifespan of the protein by degradation).
  • Long lipid-like groups added to proteins, anchor to the lipid bilayer.
  • Phosphorylation of serine, threonine, tyrosine, and histidine residues, regulating protein activity through reversible phosphorylation/dephosphorylation.
  • Glycosylation (attachment of carbohydrates) to asparagine, serine, and threonine residues; facilitating protein folding, stabilizing structure, and facilitating cell-to-cell adhesion.
  • Hydroxylation of proline and lysine residues in collagen (for triple helix formation and stabilization)
  • Methylation of histidine residues in membrane receptors.
  • Y-carboxylation of glutamate in prothrombin (essential blood-clotting factor)

Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes

• Intracellular protein lifespan varies.
• Proteins are marked for degradation through modifications of lysine side chains by adding ubiquitin.
• This process leads to protein breakdown by a specialized proteolytic machine. Subsequent ubiquitin molecules are added, forming a polyubiquitin chain.
• Proteasome recognizes the chains and degrades the protein.
• The process involves ATP.