January 21 and 23 Chapter 3 Protein structure, function and regulation

Overview of Proteins

  • Proteins are essential macromolecules with various functions in cells, including:

    • Catalysis: Enzymes that facilitate chemical reactions by breaking or forming bonds.

    • Structural Components: Provide mechanical support and shape to cells and tissues.

    • Transport Proteins: Move ions or small molecules across cell membranes.

    • Motility: Generate movement within cells or tissues, including muscle contraction.

    • Storage: Store ions and amino acids for later use.

    • Signaling: Act as signals, integrators, and transmitters in cellular communication.

    • Receptors and Ligands: Mediate interactions that trigger cellular responses.

    • Regulation: Control various cellular processes and responses to stimuli.

Types of Protein Structures

  • Proteins come in various shapes and sizes:

    • Globular Proteins: Round and soluble, typically involved in metabolic processes.

    • Filamentous Proteins: Provide structural support, such as collagen.

    • Tubular and Spherical Assemblies: Form functional complexes within cells.

    • Fibrous, Helical, and Rod-like Structures: Important for mechanical strength in tissues.

Fundamental Characteristics of Proteins

  • Polypeptide Chains: Proteins are made of linear polymers of amino acids joined by peptide bonds.

  • 3D Structure: They have unique three-dimensional structures that determine functionality.

  • Conformation: Proteins typically fold into one or a few specific conformations that are biologically active.

  • Regulation of Functionality: Protein activity can be modified through interaction with co-factors or other molecules.

Amino Acids in Proteins

  • Proteins are constructed from 20 common L-isomer amino acids.

    • Each amino acid has:

      • Characteristic Structure: Comprising an amino group, carboxyl group, and variable R group.

      • Side Chains (R Groups): Determine properties like size, charge, hydrophobicity, and reactivity.

  • Modification: Side chains can undergo various modifications post-synthesis.

Unique Roles of Certain Amino Acids

  • Certain amino acids play special roles due to unique R group properties:

    • Cysteine: Contains a sulfhydryl group that can form disulfide bonds, stabilizing protein structure.

    • Glycine: Smallest amino acid, allowing it to fit into tight spaces.

    • Proline: Rigid structure influencing protein bending and folding.

Levels of Protein Structure

  1. Primary Structure:

    • Defined by the linear sequence of amino acids in a polypeptide chain, influencing higher levels of structure.

    • Held together by covalent peptide bonds.

  2. Secondary Structure:

    • Formation of alpha helices (right-handed spirals stabilized by hydrogen bonding) and beta sheets (flat planes formed by interactions between strands).

    • Arrangement of secondary structures contributes to overall stability.

  3. Tertiary Structure:

    • Fully functional 3D structure of proteins, determined by interactions of side chains (R groups).

    • Stabilized by hydrophobic interactions, hydrogen bonds, disulfide bonds, etc.

  4. Quaternary Structure:

    • Composed of multiple polypeptide chains forming a complex (e.g., hemoglobin).

    • Subunits may be identical (homomeric) or different (heteromeric).

Protein Domains and Motifs

  • Motifs: Specific combinations of secondary structures that perform collective functions.

  • Domains: Distinct functional and structural units of proteins, typically exhibiting specific activities even when isolated.

Protein Folding and Chaperones

  • Protein Folding Process: The correct 3D structure is vital for function and is dictated by the primary sequence.

  • Chaperones: Assist in proper protein folding, preventing aggregation, and refolding misfolded proteins.

Protein Degradation and Life Span

  • Protein Stability and Degradation: Controlled through pathways including lysosomal and proteasomal degradation.

  • Regulation of Activity: Involves post-translational modifications such as phosphorylation, influencing regulation, and function, with implications in many diseases. .

Disease and Misfolding

  • Misfolded proteins can lead to severe diseases (e.g., prion diseases, Alzheimer’s, Parkinson’s).

Regulation of Protein Activity

  • Phosphorylation and Dephosphorylation: Most common regulatory mechanism, altering protein conformation and activity.

  • G-Protein Functions: GTP binding proteins operate as timers influencing protein interactions and cellular responses.