2.7 Protein Structure 3 - Tertiary and quaternary structure

Overview of Protein Structure

Proteins have multiple levels of structure: primary, secondary, tertiary, and quaternary. This note focuses primarily on the tertiary and quaternary structures, which are critical for understanding protein functionality in biological processes.

Tertiary Structure

Definition: The tertiary structure represents the overall three-dimensional shape of a fully folded protein, crucial for its function.

• Structural Domains: Comprises one or more structural domains, which are distinct regions of the protein that often serve specific functions. Each domain is characterized by its unique sequence and structure, contributing to the protein's overall functionality.

• Hydrophobic Core: The tertiary structure is typically characterized by a hydrophobic core, formed predominantly by nonpolar amino acid residues. This core constitutes about 73% of the protein's volume, providing stability through minimizing exposure to the aqueous environment.

Key Points:

• Represents one complete folded sequence of the protein.

• The folded structure is stabilized by several types of interactions, including:

  • Hydrogen Bonds: Critical for maintaining structural integrity both internally (within the protein) and externally (with surrounding molecules).

  • Van der Waals Forces: These weak, non-covalent attractions, which occur between closely packed atoms, help maintain the stability of the hydrophobic core and overall protein structure.

  • Hydrophobic Interactions: Nonpolar amino acids tend to cluster in the interior of the protein, effectively shielding themselves from water. This phenomenon is essential for the thermodynamic stability of the protein.

Folding Conformation:

• While proteins can theoretically assume billions of configurations, a stable native conformation usually exists. This native state is the biologically active form and is essential for the protein's functionality.

• The tertiary structure often incorporates elements of secondary structure, which includes:

  • α-helices: Spiral structures, typically stabilized by hydrogen bonding between backbone amides, contributing to elasticity and strength.

  • β-strands: Extended, flat regions often organized into sheets (β-sheets) formed through hydrogen bonds between different sections of peptide chains.

• Proteins may feature various combinations of α-helices and β-strands, leading to diverse structural properties, even among proteins that share similar tertiary frameworks.

Typical Tertiary Structure Motifs:

• αβ Domains: Structures characterized by a parallel β-sheet encapsulated by α-helices, contributing to stability and function.

• Parallel Barrel: Consists of a parallel β-barrel structure with surrounding alpha helices that enhances protein resilience.

• Other Notable Motifs:

  • Rossmann Fold: Frequently seen in enzymes that bind nucleotides; essential for nucleotide recognition and catalysis.

  • Greek Key Motif: Exhibited in antiparallel β-sheets, consisting of three strands linked by loops, significant for providing structural integrity in many proteins.

  • β Jelly Roll: Commonly found in virus coat proteins and legumes, serving critical structural roles, ensuring stability and integrity under various conditions.

Quaternary Structure

Definition: The quaternary structure arises from the assembly of multiple folded protein subunits, which may be the same or different in composition and sequence. This interaction among subunits is pivotal, as it can influence overall protein functionality.

• Example: Hemoglobin, which is composed of distinct α and β chains, exemplifies a protein with quaternary structure. Some proteins may form trimers or larger aggregates, illustrating varied complexities.

Structural Complexity:

• The arrangement of subunits gives rise to structurally elaborate formations, which can be crucial for biological roles. For instance:

  • Active Viruses: These entities often consist of numerous identical or non-identical protein subunits that coalesce to form protective shells enclosing their genetic material.

Stabilization Factors:

• Similar to tertiary structures, quaternary structures are maintained through:

  • Hydrophobic Interactions

  • Hydrogen Bonds

  • Salt Bridges: Electrostatic interactions between oppositely charged residues that further stabilize the subunit assembly.

Functional Sites:

• The structural composition of a protein often dictates its functionality, with specific regions (clefts or tunnels) on the surface playing critical roles in binding interactions with other molecules.

• Active and Binding Sites:

  • These sites serve as locations where substrates bind for catalysis or where regulatory molecules (effectors) can influence the protein's activity. Specific amino acids situated at these sites are crucial for mediating biological interactions essential for signaling pathways and metabolic reactions.

Specific Examples:

• Dinucleotide Binding Domain: A prevalent structure in dehydrogenases, adept at binding nucleotides essential for various metabolic processes.

• Human C-Reactive Protein: Functions through a unique pentameric structure, with specific binding sites enabling activation of the complement system, vital for immune response.

• Pyruvate Kinase: Exhibits distinct domains, including Greek key β barrels, representing the diversity of tertiary arrangements across proteins and their respective functionalities.

Conclusion

A comprehensive understanding of both tertiary and quaternary protein structures is vital as they provide insights into protein stability, functionality, and their integral roles in cellular processes.