3.1 Quaternary Structures

Focus on Protein Quaternary Structures

• Main Resources:

  • Biochemistry, Stryer - 8th Edition

  • Principle of Biochemistry, Nelson & Cox - 6th Edition

  • The Protein Data Bank (www.ebi.ac.uk/pdbe)

Learning Outcomes

• Recognize the levels of protein structure/organization

• Describe how larger structures can be formed by self-assembly of protein subunits

• Understand the three different types/classes of proteins:

  • Soluble proteins

  • Multi-subunit complexes

Protein Structure – Primary Structure

• Primary Structure: Sequence of amino acids in a peptide chain

• Key aspects:

  • Atomic composition, arrangement, and chemical bonds

  • Directionality: N-terminus to C-terminus

• Example Sequence: Ala-Val-Asp-Leu-Ser-His-Phe-Leu-Lys-Glu-Lys (AVDLSHFLKEK)

Protein Structure – Secondary Structure

• Secondary Structure: Arrangement of localized regions within 3D conformation

• Main forms include:

  • Helices

  • Sheets

• Defined by hydrogen bonding, contributing to stability and overall structure

Protein Structure – Tertiary Structure

• Tertiary Structure: Overall 3-D organization and folding of the protein

• Proteins utilize common structural motifs for folding:

  • Tim Barrel, barrel, Rossman fold, globin fold

• The specific fold correlates with protein function

• Example: Whale Myoglobin vs. Human Myoglobin

Protein Structure: Quaternary Structure

• Quaternary Structure: Assembly of multiple polypeptide chains

  • A single polypeptide chain is termed a subunit

• Arrangement of these subunits leads to complexes known as oligomers/multimers

• Interactions occur through amino acid side chains

• Examples: Myoglobin, Haemoglobin

Page 7: Importance of Quaternary Structures

• Many enzymes function as multi-subunit complexes (quaternary structure)

• Changes in quaternary structure can influence bioactivity and physiological function

• Examples of multi-protein complexes in biological systems

Soluble/Globular Proteins

• Characteristics of water-soluble proteins:

  • Exterior: hydrophilic (water-attracting)

  • Interior: hydrophobic (water-repelling)

• Example: Haemoglobin, which has a hydrophobic core essential for oxygen transport

Nomenclature of Oligomers/Multimers

• Naming conventions for subunits:

  • 1 = monomer, 2 = dimer, 3 = trimer, 4 = tetramer,

  • Continuing up to 20 = eicosamer

• Subunits: 1 subunit = monomer; multiple subunits form oligomers (multimers)

Type of Quaternary Structures: Dimers

• Dimers: Composed of 2 subunits

  • Homodimers: Identical subunits (A = B)

  • Examples of naming: A2 or a2

• Dimer interface involves protein/protein interactions through amino acid side chains

Type of Quaternary Structures: Dimers

• Heterodimers: Composed of 2 different subunits (A ≠ B)

• Naming examples: ab or AB

• Dimer interface involves protein/protein interactions, vital for function

Examples of Dimers

• Homodimer: Alcohol Dehydrogenase (ADH)

• Heterodimer: Insulin (A ≠ B)

• Structural stabilization via S-S bonds and hydrogen bonding between side chains

Type of Quaternary Structures: Trimers

• Trimers: Composed of 3 subunits

  • Homotrimer: A = B = C (identical)

  • Heterotrimer: A, B, C (different subunits)

Examples of Trimers

• Example of Homotrimer: SARS-CoV-2 Spike Protein G

• Example of Heterotrimer: Various proteins binding/acting in specific contexts

Types of Tetramers

• Tetramers: Composed of 4 subunits

  • Homotetramer: Identical subunits

  • Heterotetramer: Dimer of dimer arrangement

Examples of Tetramers

• Homotetramer Example: GAP dehydrogenase

Multimers/Oligomers – Multiple Subunits

• F0 F1 ATP Synthase:

  • Composed of 24 sub-units involved in ATP synthesis via proton gradient

  • Different chains: F0 = 3 chains (integral membrane protein), F1 = 5 chains (peripheral membrane protein)

Multimers/Oligomers - Features

• Description of functions in bacterial flagella and components of power transmission

• Diverse assembly of numerous proteins forming structural filaments, but no specifics available in the text

Complex Quaternary Structure

• Example: Human Rhinovirus forming a 240-mer complex

• Structural arrangement: 60 x 4 subunits in icosahedral (20-faced polygon) configuration

Polymerization

• Discussion of Linear chains and helical structures, indicating structural diversity in proteins

Summary

• Recap of protein structures:

  • Primary: Sequence of amino acids

  • Secondary: Local folding patterns

  • Tertiary: Overall folded structure

  • Quaternary: Assemblies of multiple subunits

• Types of proteins: Soluble, Fibrous, Membrane