Lecture #4: Protein Structure and Function, Part 1

Flashcards covering key concepts from Protein Structure and Function, Part 1 (Chapter 3, pages 70-95).

What are the four levels of protein structure?

Primary, secondary, tertiary, and quaternary structure.

What does primary structure refer to?

The linear sequence of amino acids linked by peptide bonds, with the sequence information encoded in DNA.

What kind of bond links amino acids in the primary structure?

Peptide bonds formed by a dehydration reaction between the C-terminus of one amino acid and the N-terminus of the next.

What is secondary structure?

Local folding into alpha-helices or beta-sheets, stabilized by hydrogen bonds between backbone amide and carbonyl groups.

Describe an alpha-helix.

A right-handed helix with about 3.6 amino acids per turn; stabilized by backbone hydrogen bonds; R groups project outward; proline is usually excluded.

Describe a beta-sheet.

Two or more beta strands arranged in antiparallel or parallel orientation; stabilized by backbone hydrogen bonds; side chains project above and below the sheet.

What is a beta turn?

A four-residue turn that reverses the polypeptide direction; glycine and proline are commonly found in beta turns.

What is tertiary structure?

The overall three-dimensional conformation of a single polypeptide, stabilized by hydrophobic and van der Waals interactions, hydrogen bonds, and sometimes disulfide bonds.

Which covalent bonds can stabilize tertiary structure?

Disulfide bonds between cysteine residues.

What is quaternary structure?

The arrangement and interaction of multiple polypeptide subunits to form a functional protein.

What is meant by intrinsically disordered proteins?

Proteins that lack a well-ordered native structure in isolation; highly flexible and can interact with multiple partners; may fold upon interaction.

What are the four broad structural categories of proteins?

Globular proteins, fibrous proteins, integral membrane proteins, and intrinsically disordered proteins.

What does planar peptide bond imply for protein folding?

Peptide bonds are planar with limited rotation; the only flexibility comes from rotation around the fixed planes of adjacent bonds (phi and psi); trans is dominant (~99.97% unless the preceding residue is proline).

What are protein motifs?

Regular combinations of secondary structures with specific functions, often encoded by conserved sequence motifs (e.g., coiled-coil, EF-hand, zinc-finger).

What are protein domains?

Distinct regions within proteins; functional domain (activity), structural domain (stable unit), and topological domain (spatially defined regions such as membrane-spanning domains).

What does modular nature of protein domains refer to?

Many proteins have multiple domains; domains can be combined modularly to create diverse proteins; examples include EGF domains and tissue plasminogen activator.

What is quaternary structure in terms of protein interactions?

How subunits interact to form multiprotein or supramolecular complexes.

What are four common visualization methods for protein structure?

Cα backbone trace, ball-and-stick, ribbon diagram, and water-accessible surface model.

What is the role of molecular chaperones in protein folding?

They act as helper proteins to prevent nonselective interactions and assist proper folding; examples include HSP70, HSP90, and chaperonins.

How does the Hsp70 chaperone cycle work in brief?

Hsp70 binds an unfolded protein; ATP hydrolysis locks the region in place with help from co-chaperones; ATP is exchanged for ADP; the properly folded substrate is released.

What is the role of Hsp90 in folding?

Hsp90 cycles through conformational states driven by nucleotide binding and hydrolysis to assist client protein folding and release.

What is a chaperonin and its function?

A folding chamber that isolates unfolded proteins to provide an environment for correct folding, reducing interference from other macromolecules.

What is proline cis/trans isomerization and its significance?

Peptide bonds adjacent to proline can be cis or trans; ~5% of peptide bonds with P2 = proline are cis; proline isomerases catalyze the switch to facilitate folding and can regulate activity.

How can misfolded proteins contribute to disease?

Misfolded proteins can aggregate into amyloid fibrils and plaques, implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's, and prion-like diseases.

What determines the native conformation of a protein?

The native state is the conformation with the lowest free energy (G) under given conditions.

What drives protein folding into a compact core?

Hydrophobic residues cluster into the folded core, driven by the hydrophobic effect; charged/polar residues stabilize surfaces.