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Designing this teaching tidbit has gotten completely out of hand

Designing this teaching tidbit has gotten completely out of hand. Group 1: Chemistry/Biology Interface Protein Folding. Xinnian Chen, U Conn. Alison Hill, Duke Ron Grunwald, Duke Dan Kiehart, Duke Dan Mulkey, U Conn. Carolyn Norris, Johns Hopkins Joel Schildbach, Johns Hopkins

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Designing this teaching tidbit has gotten completely out of hand

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  1. Designing this teaching tidbit has gotten completely out of hand

  2. Group 1: Chemistry/Biology Interface Protein Folding Xinnian Chen, U Conn. Alison Hill, Duke Ron Grunwald, Duke Dan Kiehart, Duke Dan Mulkey, U Conn. Carolyn Norris, Johns Hopkins Joel Schildbach, Johns Hopkins Thanks to Amy Prunuske and Brad Hyman

  3. Course: Introductory level course in which chemical foundations of biological function are described. • Students have been exposed to: • Basic chemistry of covalent and noncovalent bonds • DNA structure and sequence • Protein primary sequence is (almost always) specified by sequences in DNA. • mRNA is translated on ribosomes • Linear polypeptide chain, comes off the ribosome and begins to fold.

  4. Thus they have been exposed to: Text

  5. UNIT: INTRODUCTION TO PROTEINS Goal 1: ProteinPrimary Structure = Amino acid sequence. Goal 2: ProteinSecondary, Tertiary and Quaternary Structure Goal 3, TIDBIT: Explore HOW proteins fold

  6. 3. TIDBIT Goal: Students will begin to understand the mechanism by which proteins fold into higher order structures due to noncovalent interactions. a. Outcome: Students will be able to evaluate experimental data to decide whether or not a protein can fold spontaneously. b. Outcome:Students will be capable of predicting and describing the mechanism of disruption of protein structure by a chemical perturbant. c. Outcome: Students will recognize that protein 3D structure is required for function. (CN) (JS)

  7. Proteins with different functions have different structures • Proteins with different shapes and sizes • Proteins reproducibly fold from their primary structures • Shape determines function (JS)

  8. Even small proteins have very complex 3D structures: Ribonuclease: (RNase) is a digestive enzyme cuts RNA polymers into monomers 124 amino acids >900 atoms (not counting hydrogens!)

  9. Three different 3D representations of ribonuclease: Ribbon Diagram Highlights Secondary Structure Stick Diagram Shows the Position of Heavy Atoms (not H) Space Filling Model Features Surface Topology

  10. Hydrogen bonds stabilize protein structure, e.g., alpha helices H-bond (JS) (DM)

  11. Urea offers an opportunity to investigate the bonds that stabilize protein structure: How? (DM)

  12. How does urea interact with proteins?1) 1 minute drawing: show the interactions of 6 molecules of Urea with the polypeptide backbone on the handout (DM)

  13. 2) Think/Pair/Share: What happens when you add 8M Urea (a REALLY HIGH CONCENTRATION) to 1 µM alpha helix? Collectively choose a hypothesis for what 8M Urea does to a protein... (DPK) (DM)

  14. Next, we’ll use Urea as a probe of protein structure in an experiment (DPK)

  15. Experimental Data Ribonuclease in salt solution +/- Urea ? (DPK)

  16. Clicker Question: What do you think is the most likely effect of Urea on the STRUCTURE of the RNase? A B C Ribonuclease in dilute salt water + 8M Urea D (DPK) 0% activity 100% activity 100% activity Ribonuclease, dilute salt water, Urea removed

  17. A B C Ribonuclease in dilute salt water + 8M Urea D Clicker Vote Table discussion: rationale behind your choice (Revote if wide distribution) Class summarize why? (DPK) (RG)

  18. Cut into Pieces? Aggregate? Specific Inhibitor? You’ll learn later that good inhibitors function at nM concentrations: Remember that Urea works at M concentrations! (DPK) (RG)

  19. Christian Anfinsen: Nobel Prize in Chemistry - 1972 • One minute essay: • Based on what you’ve learned, write a that relates structure, function and reversible folding/unfolding (RG)

  20. For next class: Develop a hypothesis of protein folding that relates primary sequence to native structure and function (XC)

  21. Adios!

  22. ? Ribonuclease, dilute salt water, + “Stuff” Ribonuclease, dilute salt water, “Stuff” removed Ribonuclease in dilute salt water

  23. the “Stuff” is Urea (cute huh?): • Clicker Question: What kind of bond/force is Urea most likely to disrupt? • A. covalent B. ionic C. van der Waals D. hydrogen E. traxoline

  24. Adios!

  25. Catalog and know NC/sidechain interaction • Assessment LOCS • Manipulate strings, evaluate • Specific inteactions • Unique Structures • Next anfinsen with beta mercaptoethanol?

  26. what kind of interactions mediate these different levels of structure? Focus on noncovalent bonds and the SS bonds that stabilize it

  27. Secondary Structure: H-Bonds between atoms in the Polypeptide Backbone

  28. Structure of alpha helix and urea what happens and how?

  29. 8 8 8 8 8 1 1 1 1 1 7 7 7 7 7 2 2 2 2 2 6 6 6 6 6 3 3 3 3 3 5 5 5 5 5 4 4 4 4 4 5 possible partners 7 possible partners 3 possible partners just one option left 3 possible partners

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