2. 2 From strings to blobs How?Why? Hemoglobin I LAB 5

3. From there to here Week 3: How DNA can ‘mean’ anything; how it can pass that meaning on (replication) Week 4: How DNA can send out a ‘message’ (transcription); how that ‘message’ can be ‘translated’ into amino acids Now: How a string of amino acids is formed into a functional shape

4. 4 What do to with my string of blobs?

6. 6 Common ‘rules’ of folding (+) (-)

7. 7 Images of 3D

8. 8 Grease & beyond ‘ hiding greasy spots’ is the primary driver in protein folding maximizing the number of charge-charge and H-bonding interactions matters

9. 9 Great experiments Scrambled ribonuclease

10. Humpy Dumpy (the more tragic version)

11. 11 Sulfur + Sulfur = SulfurSulfur In a protein chain (a.k.a. polypeptide), nearby sulfur sidechains may be covalently joined http://guweb2.gonzaga.edu/faculty/cronk/biochem/images/disulfide_bond_formation.gif

12. 12 Like & unlike an egg Biochemstry, 5th ed. Berg, Tymoczko & Stryer Break disulfide (Cys-Cys through their sulfurs) Denature with heat Cool fast, allow disulfides to reform It ‘locks in’ to inactive states

13. 13 Like & unlike an egg Biochemstry, 5th ed. Berg, Tymoczko & Stryer Disconnect the disulfides Allow to re-discover its ‘comfy’ shape (re-fold on its own) Allow disulfides to re-lock Function!

14. 14 What matters today? How do we go from the ‘ticker tape’ of an mRNA to a machine? – machine = 3D object that does stuff Who shapes proteins into their shapes? Terminology: ‘folding’ Where does new functionality come from? What are the consequences of mutation?

15. 15 How does it feel* There are only about 5 ways molecular surfaces can be What are they? Amino acid ‘Easter egg hunt’ – find the one(s) that… Homepage -> “Sources” Interweb *Bob Dylan; Like a Rolling Stone

16. 30% Worksheet – Easter egg hunt 60% Hb Tutorial 10% Hb mini research What today will look like:

17. 17 Worksheet Amino acid Easter egg hunt

18. 18 http://upload.wikimedia.org/wikipedia/commons/a/a9/Amino_Acids.svg

19. 19 Question Authority To your pencils, index cards & oil-water mixes! NOT

20. 20 Ooey gooey rich & chewy inside... Protein folding, oil not mixing with water, and membrane formation all reflect the same principle In protein folding, the constraint is that the individual units are all attached to a pair of neighbors Many proteins need no further ‘instruction’ than their sequence & water to correctly assume their superhero identity

21. Inside and Outside Protein folding, oil/water, m-brane formation all same principle Protein folding- individual units attached to a pair of neighbors Many proteins need no further ‘instruction’ than sequence & water

22. If THIS is true… Pencils made of…. http://www.nano-enhanced-wholesale- technologies.com/faq/carbon-forms.htm

23. If THIS is true… Pencils made of…. Paper made of…

24. If THIS is true… Pencils made of…. Paper made of… Oil and water… Pencils, paper, oil, water…

25. 25 Your turn You ‘fold’ a protein: ProFolderPro (MCB181M_Go) Show me each solution Leave the 2nd one on screen

26. 26 Profolder features Destinations (lower right) => Folding Top: amino acid string Squares: places amino acids could go. Note ‘Undo last’ button Two spots--use one to improve upon what you did in the other Bottom: note that when you mouseOver an amino acid, it’s structure & ‘feel’ are shown

27. 27 How does yours compare?

28. Life’s blood: Hemoglobin How?Why? Let’s make sense of how this protein works today…

29. Life’s blood: Hemoglobin

30. 30 Hemoglobin: overview http://www.youtube.com/watch?v=WXOBJEXxNEo&feature=related

31. Where we are Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+diseasehttp://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

32. Where we are Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+diseasehttp://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease Hb made of four protein chains

33. Where we are Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+diseasehttp://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease Hb made of four protein chains 2 alpha chains 2 beta chains

34. Where we are Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+diseasehttp://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease Each Hb molecule has four Heme groups

35. Where we are Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+diseasehttp://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease Oxygen IS molecular, so TWO oxygen atoms

36. Hb made of four Protein chains 2 alpha chains 2 beta chains

37. You’ve seen this before: http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

38. You’ve seen this before: Amino Acid sequence http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

39. You’ve seen this before: Amino Acid sequence http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology How is this determined?

40. You’ve seen this before: Amino Acid sequence Alpha Helix http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

41. You’ve seen this before: Amino Acid sequence Alpha Helix http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology How is this determined?

42. You’ve seen this before: Amino Acid sequence Alpha Helix Folded peptide http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

43. You’ve seen this before: Amino Acid sequence Alpha Helix Folded peptide http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology How is this determined?

44. You’ve seen this before: Amino Acid sequence Alpha Helix Folded peptide Aggregation of peptides http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

45. 45 Hemoglobin: what is it? Image source: http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html

46. 46 What you’ll learn today (and potentially be quizzed on) How hemoglobin’s amino acid sequence generates its structure Why hemoglobin is a tetramer (gang of four)

47. 47 Todays assignments 30% Worksheet: easter egg hunt 60% points hemoglobin tutorial 10% points hemoglobin mini-research

48. How does it feel?* *If you don’t know who Bob Dylan is, shoot one of us now (preferably the one who’s not me)

49. 49 Hemoglobin tutorial Turn OFF Wi-Fi; QUIT safari (not close window) Read... – the instructions on each question... – the instructions on the webpage... – all the words of each question...

50. 30% Worksheet – Easter egg hunt 60% Hb Tutorial 10% Hb mini research What today will look like:

51. 51 On the relative likelihood of accidents...

52. 52 What specifically causes... A lysine to become a serine? To your codon tables!

54. Genetic disease part 2 Follow the rubric Your Disease