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Unit 2: Protein Structure, Folding, and Function

How a floppy chain of amino acids becomes an exact three-dimensional machine, what happens when folding fails, and how biologists actually see the result.

6 topics · 26 questions

Each topic is a path, not a menu: work down it in order and every question builds on the one above. Click any of them to watch the answer draw itself.

Primary and Secondary Protein Structure

  1. How it worksHow does a chain of amino acids fold into repeating alpha helices and beta sheets?
  2. How it worksWalk me through how hydrogen bonds between backbone atoms hold an alpha helix in its coil.
  3. Worked exampleFind how many possible amino acid sequences exist for a decapeptide, given 20 choices at each of its ten positions.
  4. Common mistakeWhy isn't secondary structure decided by the amino acid side chains instead of the backbone?
  5. Going furtherWhat happens to a stretch of alpha helix when a proline gets inserted into the middle of it?
Your turn1 of 2
Find how many possible amino acid sequences exist for a peptide 11 residues long, given 20 choices of amino acid at each position.

Tertiary and Quaternary Protein Structure

  1. How it worksHow do hydrophobic side chains burying themselves in the core drive a protein to fold?
  2. How it worksWalk me through how disulfide bonds lock a folded protein's shape in place.
  3. Common mistakeWhy isn't a protein's quaternary structure just several separate proteins bumping into each other?
  4. Worked exampleFind how much more sharply hemoglobin's oxygen-binding curve rises than a single-subunit protein's, given a Hill coefficient of 2.8 versus 1.0.
Your turn1 of 2
Find how many times as steeply hemoglobin's oxygen-binding curve rises compared to a single-subunit protein's, given a Hill coefficient of 3.11 for hemoglobin versus 1.06 for the single-subunit protein.

Molecular Chaperones and Assisted Folding

  1. How it worksHow does a chaperonin barrel like GroEL give a misfolded protein a private space to try folding again?
  2. How it worksWalk me through how heat shock proteins bind the exposed hydrophobic patches on a stressed protein.
  3. Common mistakeWhy isn't a chaperone protein specifying the shape its client protein folds into?
  4. Worked exampleFind how many ATP molecules two full GroEL-GroES folding cycles consume, given about 7 ATP hydrolyzed per ring per cycle.
Your turn1 of 2
Each ring of the GroEL-GroES chaperonin hydrolyzes about 8 ATP per folding cycle, and GroEL has two rings that each run through 3 full cycles. Find the total ATP consumed.

Protein Misfolding, Aggregation, and Prion Disease

  1. How it worksHow does one misfolded protein turn into a growing aggregate that damages a cell?
  2. How it worksWalk me through how a prion converts a normally folded protein into its own misfolded shape on contact.
  3. Common mistakeWhy isn't a prion disease caused by a virus, a bacterium, or any nucleic acid at all?
  4. Common mistakeWhy doesn't a cell's protein quality control system catch every misfolded protein before it aggregates?
  5. Going furtherWhat happens to a neuron's function as amyloid aggregates build up around it over years?
Your turn1 of 2
A prion disease can be transmitted between animals, much like a viral infection, yet no virus, bacterium, or nucleic acid is ever found in the infectious material. What actually explains prion transmission?

Determining Protein Structure: Crystallography, NMR, and Cryo-EM

  1. How it worksHow does firing X-rays through a protein crystal reveal where its atoms sit?
  2. How it worksWalk me through how nuclear magnetic resonance maps a protein's structure while it stays dissolved in solution.
  3. How it worksHow does flash-freezing a protein and imaging it with an electron beam let cryo-EM skip crystallization?
  4. Common mistakeWhy isn't an X-ray crystal structure a picture of the protein moving in real time?
  5. Ties togetherHow did cryo-EM's resolution jump finally let structural biologists see membrane protein complexes that never crystallize?
Your turn1 of 2
A published X-ray crystal structure shows a protein in one fixed, precise conformation. A student concludes this image is a snapshot of the protein caught moving in real time inside a cell. Why is this wrong?

Protein Domains and Modular Function

  1. How it worksHow does a folded domain act as an independent working unit within a larger protein?
  2. Going furtherWhat changes about a protein's function when two different domains get fused into one gene by evolution?
  3. Common mistakeWhy isn't a protein domain the same thing as a gene exon, even though the two often line up?
Your turn1 of 2
Over evolutionary time, a gene encoding one folded domain becomes fused with a gene encoding a different folded domain, producing a single new gene. What is the most likely functional consequence?