Framework:

1. Framework: This unit would be taught early in an Introductory Biology course as part of a broader discussion about biological macromolecules. Students would have already been introduced to major themes in biology, such as the chemistry of life (including atomic structure and types of chemical bonds). They will have just been introduced to the four major types of macromolecules: their building blocks, chemical properties, and important functional groups. The goals of this teaching unit will be to reinforce how small chemical changes in proteins can have a significant impact on the overall structure and function of a protein, using aggregation of hemoglobin in sickle cell patients as an example. The tidbit incorporates the following approaches to active learning: Think/Pair/Share, clicker questions, brainstorming, and a group worksheet that is filled out during the activity. The topic is amenable to a discussion about aspects of diversity pertaining to a disease often associated with a particular ethnic population. The tidbit contains multiple opportunities for both formative and summative assessment, for example the instructor could evaluate how well students understand the chemical properties of amino acid side chains from the worksheet exercise.

2. Summer Institute 2012 Harvard Group 1: The Interface of Biology and Chemistry Carol Bascom-Slack Carlton Cooper Michal Hallside Jacqui Johnson Course Details Gillian Phillips Eugenia Ribeiro-Hurley Erica Selva Introductory Biology 1 Week 3 of class Discussion of Macromolecules of Life

3. Expected Background Overview of Biology Atomic structure Basic Chemistry of Bonding Types of Macromolecules Hierarchy of peptide structure

4. Teachable Unit:Macromolecules of Life Goal: Appreciate the chemical diversity of macromolecules Understand the relationship between the structure of macromolecules and their function Objectives Students should be able to: Describe the structure of each of the four macromolecules of life Identify the roles of the macromolecules in a cell Describe how the structure of each macromolecule relates to its function

5. Teachable Tidbit:Sickle Cell Anemia Explained by Protein Shape Learning Goals Understand how hydrophobic and hydrophilic interactions affect protein structure Appreciate the importance of correct protein composition for proper structure Appreciate the importance of correct protein structure for proper function Learning Objectives Students should be able to: Determine if the side chain of an amino acid is mainly hydrophilic or hydrophobic in nature Describe how changes in the amino acid sequence of hemoglobin can lead to aggregation

6. Sickle Cell Anemia Symptoms: Pain in extremities and bones Fatigue Pale skin Dizziness Headaches Jaundice

7. Examination of Red Blood Cells Normal Sickle Cell Anemia

8. Hemoglobin • A principal protein component of red blood cells • Tetramer composed of two a-subunits and two b-subunits • a-subunits have 141 amino acids while the b-subunits have 146 amino acids • Each subunit carries oxygen

9. Brainstorm: What might cause a difference in the net charge of these proteins?

10. Think pair share Circle: two amino acids containing the most hydrophobic R-groups Underline: two amino acids containing the most hydrophilic R-groups

11. Think pair share: Valine (Val, V) Glutamate (Glu, E) Leucine (Leu, L) Serine (Ser, S) Threonine (Thr, T) Lysine (Lys, K) Hydrophobic amino acid R-group (side chain) Hydrophilic amino acid R-group (side chain)

12. Think pair share Valine (Val, V) Glutamate (Glu, E) Leucine (Leu, L) Serine (Ser, S) Threonine (Thr, T) Lysine (Lys, K) Hydrophobic amino acid R-group (side chain) Hydrophilic amino acid R-group (side chain)

13. Think pair share Valine (Val, V) Glutamate (Glu, E) Leucine (Leu, L) Serine (Ser, S) Threonine (Thr, T) Lysine (Lys, K) Hydrophobic amino acid R-group (side chain) Hydrophilic amino acid R-group (side chain)

14. Each blue dot=one amino acid α β α=141 amino acids β=146 amino acids α β Approximately what percentage of the 574 amino acids in hemoglobin do you think you would need to change to cause sickle cell anemia?

15. Each blue dot=one amino acid α β α=141 amino acids Β=146 amino acids α β

16. Where in this folded protein might this change have occurred?A. Near the oxygen binding siteB. At the interface between subunitsC. On the surfaceD. A and C E. A, B and C

17. These are the locations of the changed amino acids. Glutamate (hydrophilic) Valine (hydrophobic )

18. Think-pair-share Can you come up with an explanation that would link the aggregation of hemoglobin to the amino acid change?

19. Remember: An external hydrophilic amino acid is replaced with a hydrophobic one Valine (hydrophobic) Glutamate (hydrophilic)

21. Teachable Tidbit:Sickle Cell Anemia Explained by Protein Shape Learning Goals Understand how hydrophobic and hydrophilic interactions affect protein folding Appreciate the importance of the correct protein folding for proper function Learning Objectives Students should be able to: Determine if the side chain of an amino acid is mainly hydrophilic or hydrophobic in nature Describe how changes in the amino acid sequence of hemoglobin can lead to aggregation

23. Extra Information

24. For a more chemistry centric class the table below may help explain the non-polar (hydrophobic) vs. polar (hydrophilic) nature of the amino acids. There are multiple hydropathy indexes that can be used to describe the order of amino acids.