← Back to the lesson

Nerdy Jobs: Protein Crystallization

High school learnscience.org

Name Date

Predict

Proteins are tiny parts that do jobs inside your body, and one protein is much too small to see with your eyes. Could scientists grow a crystal, the kind you can see, out of a protein?

Circle one. Yes / No

Why?

Watch

  1. Nerdy Jobs S1E1, Exploring the Magic of Protein Crystallizationyoutu.be/siFfzoFv61I

Meet the scientist

Dr. Sarah Bowman

Job title. Structural biologist. Dr. Bowman directs the National High-Throughput Crystallization Center at the Hauptman-Woodward Medical Research Institute (HWI) in Buffalo, New York.

A workday. The center screens proteins for over 2,000 labs. Robots set each protein sample against 1,536 different chemical mixtures, and imagers photograph the drops for six weeks. Dr. Bowman’s own lab works on ways to grow and find tiny crystals, and uses X-ray crystallography to study proteins that hold metals.

Training. A bachelor’s degree in English literature and women’s studies, then a second bachelor’s degree in chemistry. A Ph.D. in chemistry from the University of Rochester in 2010. Seven years of research at MIT and Los Alamos National Laboratory after her Ph.D.

Word of the day

Crystallography (kris-tuh-LOG-ruh-fee). The science of crystals, how they form and how their parts are arranged.

Word partComes fromMeaning
crystallo-Greek krýstallosclear ice, rock crystal
-graphyGreek -graphíadrawing, writing, recording
  • Photography means “drawing with light.”
  • Cryo-, “icy cold,” comes from a Greek word related to krýstallos. Cryogenics is the study of extreme cold.

Bonus words. Protein (PROH-teen) comes from the Greek prōteîos, “primary.” Diffraction (dih-FRAK-shun) comes from the Latin diffringere, “to break into pieces.” In X-ray crystallography, the proteins in a crystal diffract X-rays into a pattern of spots.

Questions

  1. Dr. Bowman says a protein starts out as a long chain of amino acids. As the chain comes off the ribosome, it folds into a compact three-dimensional shape. The order of amino acids in the chain comes from a gene. How does a gene connect to the job a protein does?

    Hint. Trace the steps from the gene, to the order of amino acids, to the folded shape, to the job.

  2. Hemoglobin carries oxygen on iron atoms, one inside each of its four heme groups. Dr. Bowman says hemoglobin has one shape with oxygen bound and a slightly different shape without oxygen. Why would a structural biologist want structures of hemoglobin both with and without oxygen?

    Hint. One structure shows one shape. What could comparing two shapes reveal about how hemoglobin loads and unloads oxygen?

  3. X-ray crystallography relies on many copies of a protein lined up in the same direction inside a crystal. Some proteins have floppy, flexible parts. Why would a flexible protein be hard to study with X-ray crystallography?

    Hint. Picture thousands of copies of the protein packed in a crystal. What happens if the flexible parts point a different way in each copy?

  4. The main protease of SARS-CoV-2, the virus that causes COVID-19, cuts the virus’s other proteins into working pieces. Dr. Bowman says the main protease looks different when a drug is bound. Nirmatrelvir, a COVID-19 drug that blocks the main protease, was designed from X-ray structures of the protease with another drug bound. Why would drug designers want structures of the protease with a drug bound, instead of the empty protease alone?

    Hint. What does a drug-bound structure show that an empty one can’t?

Claim, evidence, reasoning

In sickle cell hemoglobin, a change in the hemoglobin gene swaps one amino acid. Glutamate at position 6 of hemoglobin’s beta chain becomes valine. When the changed hemoglobin has no oxygen bound, the molecules stick together into stiff fibers inside red blood cells and bend the cells into a sickle shape. How can a change in one gene change the job hemoglobin does? Make a claim, back it with evidence and explain your reasoning.

Hint. Follow the chain from gene, to amino acid, to protein shape, to what the protein does.

Claim

Evidence

Reasoning

Going further

  1. Dr. Bowman’s center runs lysozyme, the same protein from the episode, as a control in its monthly screening runs. Scientists already know lysozyme grows crystals. Why would a crystallization center test lysozyme each month when scientists already know lysozyme grows crystals?

    Hint. Imagine the lysozyme drops stopped growing crystals one month. What would that tell the center?

Exit ticket

Dr. Bowman says the more scientists know about what things look like, the better they understand how they work. What steps lead from a protein in a drop to a medicine that blocks the protein?

Hint. Start with the crystal in the drop. End with a drug designed to fit the protein.

Sources