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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

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

Thanks to Amy Prunuske and Brad Hyman


Designing this teaching tidbit has gotten completely out of hand

  • 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.


Designing this teaching tidbit has gotten completely out of hand

Thus they have been exposed to:

Text


Designing this teaching tidbit has gotten completely out of hand

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


Designing this teaching tidbit has gotten completely out of hand

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)


Designing this teaching tidbit has gotten completely out of hand

Proteins with different

functions have different structures

  • Proteins with different shapes and sizes

  • Proteins reproducibly fold from their primary structures

  • Shape determines function

(JS)


Designing this teaching tidbit has gotten completely out of hand

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!)


Designing this teaching tidbit has gotten completely out of hand

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


Designing this teaching tidbit has gotten completely out of hand

Hydrogen bonds stabilize protein structure, e.g., alpha helices

H-bond

(JS)

(DM)


Designing this teaching tidbit has gotten completely out of hand

Urea offers an opportunity to investigate the bonds that stabilize protein structure: How?

(DM)


Designing this teaching tidbit has gotten completely out of hand

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)


Designing this teaching tidbit has gotten completely out of hand

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)


Designing this teaching tidbit has gotten completely out of hand

Next, we’ll use Urea as a probe of protein structure in an experiment

(DPK)


Designing this teaching tidbit has gotten completely out of hand

Experimental Data

Ribonuclease

in

salt solution

+/- Urea

?

(DPK)


Designing this teaching tidbit has gotten completely out of hand

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


Designing this teaching tidbit has gotten completely out of hand

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)


Designing this teaching tidbit has gotten completely out of hand

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)


Designing this teaching tidbit has gotten completely out of hand

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)


Designing this teaching tidbit has gotten completely out of hand

  • For next class: Develop a hypothesis of protein folding that relates primary sequence to native structure and function

(XC)


Adios

Adios!


Designing this teaching tidbit has gotten completely out of hand

?

Ribonuclease,

dilute salt water,

+ “Stuff”

Ribonuclease,

dilute salt water,

“Stuff” removed

Ribonuclease

in

dilute salt water


Designing this teaching tidbit has gotten completely out of hand

  • 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


Designing this teaching tidbit has gotten completely out of hand

  • Adios!


Designing this teaching tidbit has gotten completely out of hand

  • Catalog and know NC/sidechain interaction

  • Assessment LOCS

  • Manipulate strings, evaluate

  • Specific inteactions

  • Unique Structures

  • Next anfinsen with beta mercaptoethanol?


Designing this teaching tidbit has gotten completely out of hand

what kind of interactions mediate these different levels of structure?

Focus on noncovalent bonds and the SS bonds that stabilize it


Designing this teaching tidbit has gotten completely out of hand

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


Designing this teaching tidbit has gotten completely out of hand

Structure of alpha helix and urea

what happens and how?


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