Protein Structure Overview

Protein Structure

• Proteins are composed of amino acids linked by peptide bonds
• Peptide bond formation involves a covalent bond between the carboxyl group of one amino acid and the amino group of another
• Peptide bonds exhibit resonance, resulting in a partial double-bond character and limiting rotation
• Torsion angles (φ and ψ) are crucial for protein structure, and steric constraints constrain possible combinations of these angles
• The Ramachandran plot visually represents allowed combinations of phi and psi angles for amino acid residues
• Stability of folded proteins primarily relies on noncovalent interactions (van der Waals forces, hydrogen bonds, and salt bridges)
• Covalent interactions (peptide bonds, and disulfide bridges) also contribute to stabilization
• Secondary structure includes common elements like alpha helices and beta sheets
• Alpha helices are characterized by hydrogen bonds between every fourth amino acid residue creating a right-handed helix
• Beta sheets consist of extended planar structures, held together by hydrogen bonds between adjacent polypeptide backbones
• The arrangement of secondary structural elements into specific motifs (e.g., four-helix bundles, beta barrels) contributes to tertiary structure
• Tertiary protein structure is the three-dimensional arrangement of the polypeptide chain
• The folding of proteins relies on interactions of hydrophilic and hydrophobic amino acid residues with the surrounding aqueous environment
• Membrane proteins have specific structural features to interact with hydrophobic membrane interiors
• Proteins maintain dynamic stability through conformational changes
• Protein stability is influenced by post-translational modifications
• Proteins are composed of various domains and motifs, which contribute to specific functions.

Protein Domains

• Globular proteins often consist of several domains
• Domains frequently fold independently, retaining functional activity
• A limited number of protein folds exists with varying amino acid sequences but similar structural characteristics

Protein Motifs

• Sequence motifs involve specific amino acid sequences with characteristic purposes
• Zinc finger motifs are examples of sequence motifs often in DNA-binding proteins
• Structural motifs are groups of sequential secondary structures; domains are comprised of motifs
• Four-helix bundles and beta-barrels are examples of structural motifs

Classes of Domain Folds

• Alpha domains consist solely of alpha helices
• Beta domains entirely composed of beta sheets, typically antiparallel
• Alpha/beta domains contain both alpha helices and beta sheets, often with specific arrangements, e.g. alpha/beta barrel
• Alpha+beta domains comprise both alpha-helices and beta-sheets,without a specific arrangement pattern
• Cross-linked domains, often have little to no secondary structure, their folding stabilized via disulfide bridges or metal ions

Quaternary Structure

• Quaternary structure refers to the arrangement of multiple polypeptide chains, known as subunits, within a single protein complex
• Protein complexes can exhibit various symmetries (e.g., dimer, trimer, tetramer) based on subunit arrangements
• Intermolecular interactions (e.g., hydrophobic and hydrogen interactions, salt bridges) ensure that subunits come together
• Multiple identical or distinct subunits assemble into higher-order structures. Each protein has a unique quaternary structure

Protein Flexibility

• Protein flexibility is crucial for their function
• Fluctuations, collective motions of neighbouring groups of atoms, domain movements, and ligand-induced changes in conformation are examples of protein flexibility
• Dynamic movements of the protein contribute to substrate binding, catalysis, and signalling

Protein Stability

• Protein chains are only marginally stable, which is essential for flexibility and function
• Disruption of protein structure can occur via thermal or chemical denaturation
• Post-translational modifications (e.g., glycosylation, phosphorylation) can affect protein stability and function

Explore the fundamental concepts of protein structure, including amino acids, peptide bonds, and the significance of torsion angles. This quiz will test your understanding of the secondary structures such as alpha helices and beta sheets, as well as the stabilization of folded proteins through various interactions.