Protein Structure and Forces

Protein Structure

• Proteins are large, complex molecules vital for numerous cellular functions.
• Their function hinges on their specific three-dimensional shape.
• The sequence of amino acids in a polypeptide chain determines the protein's overall structure.

Forces Influencing Protein Structure

• Hydrogen bonds form between peptide groups in the protein backbone.
• Hydrogen bonds form between side chains.
• Hydrophobic interactions occur between non-polar side chains.
• Hydrophilic interactions occur between polar side chains.
• Ionic bonds form between oppositely charged side chains.
• Disulfide bonds link cysteine side chains.

Secondary Structures

• Alpha-helix: A predominantly right-handed helical structure stabilized by hydrogen bonds between the N-H group of one peptide bond and the C=O group of another, typically four amino acids apart.
• Average amino acids per helix is around 11, though this can vary up to 53.
• Beta-sheet: A pleated sheet structure in which multiple β-strands are arranged parallel or anti-parallel. Hydrogen bonds between the polypeptide backbone of adjacent strands stabilize the structure.
• Parallel and anti-parallel beta strands are two possible variations.
• Average amino acids per sheet is between 2-15, with an average of 6.

Tertiary Structures

• The overall 3D structure of a polypeptide chain.
• The arrangement of secondary structures.
• Proteins often contain hydrophobic amino acids nestled inside the folded structure and hydrophilic amino acids on the outside, to facilitate water solubility.
• Myoglobin and hemoglobin are examples of proteins with a predominant alpha-helical structure and a compact shape.
• Concanavalin A is an example of a protein with predominantly beta-sheet structure.
• Supersecondary structures/motifs are formed by combinations of secondary structures.

Quaternary Structures

• The structure resulting from the interaction of multiple polypeptide chains.
• Proteins with more than one polypeptide chain are called oligomeric.
• Individual chains within an oligomeric structure are called subunits or monomers.
• Examples: Haemoglobin, Myoglobin, Muscle creatine kinase.

Central Dogma of Protein Folding

• Primary structure dictates the tertiary structure.
• Protein folding is a spontaneous process.
• Local secondary structures form a nucleus, around which the rest of the protein folds.
• Molecular chaperones aid protein folding, especially under stress conditions.

Selected Protein Structures

• Fibrous Proteins:
  • Primarily structural proteins.
  • Examples: Keratin, Collagen, Silk.
• Globular Proteins:
  • Perform metabolic functions including transport, catalysis (e.g., enzymes), hormone function.
  • Examples: Myoglobin, Hemoglobin.

Denaturing Proteins

• Proteins denature when bonds maintaining their shape are broken.
• Temperature, pH, or salt concentration changes can cause denaturation.
• Denatured proteins lose function and often become insoluble.
  • Fibrous Proteins: lose structural strength when denatured
  • Globular Proteins: become insoluble and inactive.

Myoglobin

• Myoglobin's structure was determined through x-ray crystallography.
• Contains 153 amino acids with 75% in alpha-helix and 8 helix segments (A to H).
• Its compact shape facilitates oxygen binding.
• It has a prosthetic group, haem, essential for oxygen transport

Hemoglobin

• Haemoglobin is a critical oxygen-transport protein.
• It has four protein chains (2 alpha and 2 beta). Each subunit can carry one oxygen molecule, making its capacity to carry oxygen high.
• Each subunit has 7-8 helical segments like myoglobin.
• Its quaternary structure enables cooperative oxygen binding and release.
• Haemoglobin has different conformations (R and T states) related to oxygen binding affinity.
• Changes in haemoglobin structure cause conditions like sickle-cell anemia.

Differences between Collagen and Haemoglobin