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

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From strings to blobsHow? Why?

Hemoglobin I

LAB 5

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

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What do to with my string of blobs?

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Common ‘rules’ of folding

(+)

(-)

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Images of 3D

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Grease & beyond• ‘hiding greasy spots’ is the primary driver

in protein folding• maximizing the number of charge-charge

and H-bonding interactions matters

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Great experimentsScrambled ribonuclease

Humpy Dumpy (the more tragic version)

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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

http://guweb2.gonzaga.edu/faculty/cronk/biochem/images/disulfide_bond_formation.gif

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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

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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!

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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?

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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

• 30% Worksheet – Easter egg hunt• 60% Hb Tutorial• 10% Hb mini research

What today will look like:

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WorksheetAmino acid Easter egg hunt

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

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

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Question AuthorityTo your pencils, index cards & oil-water

mixes!NOT

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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

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

If THIS is true…• Pencils made of….

http://www.nano-enhanced-wholesale-technologies.com/faq/carbon-forms.htm



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

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

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Your turn• You ‘fold’ a protein: ProFolderPro

(MCB181M_Go)• Show me each solution • Leave the 2nd one on screen

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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

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How does yours compare?

Life’s blood: Hemoglobin

How? Why?

Let’s make sense of how this protein works today…

Life’s blood: Hemoglobin

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Hemoglobin: overview

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

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

Where we are

Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

Where we are


Hb made of fourprotein chains


Where we are


Hb made of fourprotein chains

2 alpha chains2 beta chains


Where we are


Each Hb moleculehas four Heme groups


Where we are


Oxygen IS molecular, so TWO oxygen atoms


Hb made of fourProtein chains

2 alpha chains2 beta chains

You’ve seen this before:

http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology



You’ve seen this before:Amino Acid sequence




You’ve seen this before:Amino Acid sequence


How is this determined?



You’ve seen this before:Amino Acid sequenceAlpha Helix




You’ve seen this before:Amino Acid sequenceAlpha Helix





You’ve seen this before:Amino Acid sequenceAlpha HelixFolded peptide




You’ve seen this before:Amino Acid sequenceAlpha HelixFolded peptide





You’ve seen this before:Amino Acid sequenceAlpha HelixFolded peptideAggregation of peptides




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Hemoglobin: what is it?

Image source: http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html

http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html

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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)

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Todays assignments30% Worksheet: easter egg hunt60% points hemoglobin tutorial10% points hemoglobin mini-research

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)

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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...

• 30% Worksheet – Easter egg hunt• 60% Hb Tutorial• 10% Hb mini research

What today will look like:

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On the relative likelihood of accidents...

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What specifically causes...

• A lysine to become a serine?• To your codon tables!

• Genetic disease part 2• Follow the rubric

Your Disease

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

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