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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


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


  • 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.


Thus they have been exposed to: foundations of biological function are described.

Text


UNIT: INTRODUCTION TO PROTEINS foundations of biological function are described.

Goal 1: ProteinPrimary Structure = Amino acid sequence.

Goal 2: ProteinSecondary, Tertiary and Quaternary Structure

Goal 3, TIDBIT: Explore HOW proteins fold


3. TIDBIT Goal: foundations of biological function are described.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)


Proteins with different foundations of biological function are described.

functions have different structures

  • Proteins with different shapes and sizes

  • Proteins reproducibly fold from their primary structures

  • Shape determines function

(JS)


Even small proteins have very complex 3D structures: foundations of biological function are described.

Ribonuclease: (RNase) is a digestive enzyme

cuts RNA polymers into monomers

124 amino acids

>900 atoms (not counting hydrogens!)


Three different 3D representations of ribonuclease: foundations of biological function are described.

Ribbon Diagram Highlights Secondary Structure

Stick Diagram Shows the Position of Heavy Atoms (not H)

Space Filling Model Features Surface Topology


Hydrogen bonds stabilize protein structure, foundations of biological function are described.e.g., alpha helices

H-bond

(JS)

(DM)


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

(DM)


How does urea interact with proteins? stabilize protein structure: How?1) 1 minute drawing: show the interactions of 6 molecules of Urea with the polypeptide backbone on the handout

(DM)


2) Think/Pair/Share: What happens when stabilize protein structure: How?

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)



Experimental Data experiment

Ribonuclease

in

salt solution

+/- Urea

?

(DPK)


Clicker Question: experiment

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


A experiment

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)


Cut into Pieces? Aggregate? Specific Inhibitor? experiment

You’ll learn later that good inhibitors function at nM concentrations:

Remember that Urea works at M concentrations!

(DPK)

(RG)


Christian Anfinsen: experiment

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)


(XC)


Adios
Adios! relates primary sequence to native structure and function


? relates primary sequence to native structure and function

Ribonuclease,

dilute salt water,

+ “Stuff”

Ribonuclease,

dilute salt water,

“Stuff” removed

Ribonuclease

in

dilute salt water


  • the “Stuff” is Urea (cute huh?): relates primary sequence to native structure and function

  • 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


  • Adios! relates primary sequence to native structure and function


  • Catalog and know NC/sidechain interaction relates primary sequence to native structure and function

  • Assessment LOCS

  • Manipulate strings, evaluate

  • Specific inteactions

  • Unique Structures

  • Next anfinsen with beta mercaptoethanol?


what kind of interactions mediate these different levels of structure?

Focus on noncovalent bonds and the SS bonds that stabilize it



Structure of alpha helix and urea Polypeptide Backbone

what happens and how?


8 Polypeptide Backbone

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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