JW

Notes on Four Levels of Protein Structure and Visualization

Four levels of protein structure (non-hierarchical)

  • Proteins are described by four levels of structure. NOTE - these are not hierarchical!!

  • The four levels are:

    • Primary Protein Structure: Sequence of a chain of amino acids.

    • Secondary Protein Structure: Local folding of the polypeptide chain into helices or sheets.

    • Tertiary Protein Structure: Three-dimensional folding pattern of a protein due to side chain interactions.

    • Quaternary Protein Structure: Protein consisting of more than one amino acid chain.

  • All proteins are made of amino acids connected by covalent bonds.

Primary Protein Structure

  • The primary structure of a protein is just the linear string of amino acids.

  • This is described as the fundamental sequence that determines higher levels of structure.

Secondary Protein Structure

  • Proteins fold to create bonds that stabilize the structure.

  • Because proteins exist in water, hydrophobic amino acids need to be secluded; non-covalent bonds form depending on the position and chemistry of each amino acid.

  • These interactions between backbone atoms (and sometimes side chains) give rise to secondary structure.

  • Common secondary structures include:

    • α-helix (α-helix)

    • β-pleated sheet (β-pleated sheet)

  • These interactions between backbone atoms in turn create helices and sheets.

Shielding hydrophilic atoms in hydrophobic spaces and backbone interactions

  • A hydrophilic backbone in a hydrophobic region would be unstable unless shielded.

  • The backbone atoms are connected to the side chains; in transmembrane or hydrophobic environments, backbone amine and carboxyl groups need stabilization.

  • Backbones pair up with nearby atoms to shield hydrophilic atoms in hydrophobic spaces via several common interactions (frontier examples shown in the source):

    • Backbone to backbone hydrogen bonds (e.g., stabilizing helices and sheets)

    • Backbone to side chain hydrogen bonds

    • Side chain to side chain hydrogen bonds

Tertiary Protein Structure

  • Tertiary structure refers to the three-dimensional folding pattern of a protein due to side chain interactions.

  • These interactions depend on the chemistry of each amino acid and the environment (e.g., hydrophobic vs. hydrophilic surroundings).

  • In membranes or hydrophobic spaces, backbone and side chain interactions help shield hydrophilic atoms to maintain stability.

  • The interactions described above (backbone-backbone, backbone-side chain, side chain-side chain) contribute to the overall three-dimensional shape of the protein.

  • The stability of the tertiary structure arises from the cumulative effect of these non-covalent interactions (and sometimes covalent disulfide bonds in some proteins, though not explicitly mentioned in the transcript).

Quaternary Protein Structure

  • When multiple primary structures (polypeptide chains) interact, the resulting assembly is a quaternary structure.

  • Examples discussed:

    • Dimer of the CAP protein: dimer formed by interaction between a single, identical binding site on each monomer.

    • Tetramer of neuraminidase protein: tetramer formed by interactions between two nonidentical binding sites on each monomer.

  • Terms:

    • Monomer: single polypeptide chain

    • Dimer: two polypeptide chains

    • Tetramer: four polypeptide chains

  • These assemblies illustrate how multiple subunits come together to form a functional protein complex.

Protein structure displays and visualization

  • Proteins are displayed in a few ways, depending on which information is most helpful:

    • Backbone model

    • Ribbon model

    • Space-filling model

  • These displays help relate structure to function and give intuition about folding and interactions.

  • Practical note: Cartoons of space-filling models are often used to illustrate relationships between structure and function.

Summary of key points and connections

  • The video/module aims to:

    • Describe the four levels of protein structure in chemical terms.

    • Explain how secondary structures protect hydrophilic atoms in hydrophobic spaces.

    • Recognize several ways to present protein structures visually.

  • All proteins are built from amino acids linked by covalent bonds.

  • The primary structure is the linear amino acid sequence; this sequence determines higher-order structure.

  • Proteins fold to stabilize their structure via various non-covalent interactions, with hydrophobic effects driving shielding of hydrophilic atoms in nonpolar environments.

  • Secondary structures (α-helix and β-pleated sheet) arise from backbones forming hydrogen bonds in a regular pattern.

  • Tertiary structure results from the three-dimensional arrangement driven by side-chain interactions, within the constraints set by the hydrophobic/hydrophilic context.

  • Quaternary structure emerges when multiple polypeptide chains assemble into a functional unit; examples include homodimers and heterotetramers.

  • Visualization tools (backbone, ribbon, space-filling models) aid in understanding structure-function relationships.