Protein Structure and Classification

Protein Structure

• Proteins are organic compounds containing carbon (C), hydrogen (H), oxygen (O), phosphorus (P), and sulfur (S).
• They are polymers of amino acids joined together by peptide bonds.
• Proteins have different levels of organization: primary, secondary, tertiary, and quaternary.

Protein Definition

• Proteins are high molecular weight mixed polymers of amino acids joined together by peptide linkages.

Overview of Protein Structure

• Configuration: The geometric relationship between a set of atoms, e.g., distinguishing L-amino acid from D-amino acid.
• Conformation: The spatial arrangement of atoms in a protein.
• Most stable conformations exist thermodynamically.
• Protein structure is stabilized by weak interactions.

Classification of Proteins

• Proteins can be classified based on function, chemical composition, structure/shape, and nutritional value.

Classification Based on Function

• Hormonal: Insulin, Glucagon
• Enzymatic: Amylase, catalase, trypsin
• Structural: Keratin, collagen, elastin
• Defensive: Antibodies
• Storage: Ferritin, casein in breast milk
• Transport: Hemoglobin
• Receptor: Proteins on cell membrane
• Contractile: Actin, myosin

Classification Based on Chemical Composition

• Simple: Globular (albumins, globulins, glutelins, prolamines, histones, and other globulins), Scleroproteins (collagens, elastins, and keratins)
• Conjugated: Nucleoproteins, glycoproteins, lipoproteins, chromoproteins, metalloproteins, phosphoproteins
• Derived: Primary, secondary, proteoses, peptones, polypeptides, peptides, proteans, and metaproteins

Conjugated Proteins

• Phosphoprotein: Casein of milk, vitellin of egg yolk
• Lipoprotein: Membrane proteins
• Metalloprotein: Nitrate reductase
• Nucleoprotein: Telomerase
• Glycoprotein: FSH
• Chromoprotein: Hemoglobin in cytochrome

Classification Based on Structure/Shape

• Fibrous proteins: Collagen, keratin, myosin
• Globular proteins: Insulin, hemoglobin, DNA & RNA polymerase
• Intermediate proteins: Blood clotting proteins like fibrinogen

Classification Based on Nutritional Value

• Complete: Proteins in milk, eggs, fish, and meat
• Incomplete: Nuts, beans, cereals
• Partially Incomplete: Proteins from wheat, rice and corn

Levels of Protein Structure

• Primary (1°): Linear sequence of amino acids in a polypeptide chain, linked by peptide bonds (N-terminal to C-terminal).
•  Secondary (2°): Local folding patterns—α-helix (spiral) and β-sheet (folded). Hydrogen bonds within the backbone stabilize these patterns.
•  Tertiary (3°): Overall 3D arrangement of the polypeptide chain. Interactions between amino acid side chains (R groups) determine the 3D structure, including hydrophobic interactions, hydrogen bonds, disulfide bonds, and ionic bonds.
•  Quaternary (4°): Arrangement of multiple polypeptide chains (subunits) in a protein complex. Interactions between subunits determine the final structure. Examples include hemoglobin (4 polypeptide chains).

Protein Folding

• Peptide bonds allow rotation, allowing proteins to fold.
• Weak non-covalent interactions (hydrogen bonds, hydrophobic interactions, ionic bonds) maintain the protein's 3D shape.
• Protein folding occurs in the cytosol.

Protein Structure Summary

• Regular folding patterns (α-helix, β-sheet) combine for domains and other specific structures.
• Turns and loops connect the secondary structures in folded proteins.
• β-turns are tight turns, typically 4 amino acids in length. -Disulfide bridges can connect cysteine amino acids, stabilizing tertiary structure and contribute to protein function
• Protein folding ensures correct spatial arrangement for proper function.

Tertiary Structure Stabilization

• Important interactions for stabilizing tertiary structures include:
  • Hydrophobic effect
  • Hydrogen bonds
  • Ionic bonds
  • Disulfide bonds
  • and van der Waals forces.

Quaternary Structure

• The arrangement of multiple polypeptide chains (subunits) in a protein complex.
• Stabilized by weak forces.
• Examples include hemoglobin and some enzymes.

Subunits and Symmetry

• Protein subunits can have various symmetries like rotational and dihedral.
• Hemoglobin is a tetramer with two α and two β subunits.

Key Concepts

• Tertiary and quaternary structures result from folding of primary and secondary structures in three dimensions.
• Larger proteins often have multiple folded domains.
• Folding of hydrophilic proteins minimizes contact with water, hydrophobic side chains are in the interior of the protein, and hydrophilic amino acids on the outer surface exposed to water.
• Protein folding brings specific groups into position to participate in functions like carrying oxygen in hemoglobin by tertiary and quaternary structure.

Domains

• Domains are independently folding units within a larger protein structure.
• Domains can have different functions.

Summary of Structural Levels

• Primary structure: The amino acid sequence.
• Secondary structure: Local folding patterns in a protein.
• Tertiary structure: The overall 3D structure of a single polypeptide chain.
• Quaternary structure: The arrangement of multiple polypeptide subunits in a protein complex.