2 from strings to blobs how?why? hemoglobin i lab 5
TRANSCRIPT
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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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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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
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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
18http://upload.wikimedia.org/wikipedia/commons/a/a9/Amino_Acids.svg
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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
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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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Hemoglobin: overview
http://www.youtube.com/watch?v=WXOBJEXxNEo&feature=related
Where we are
Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease
Where we are
Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease
Hb made of fourprotein chains
Where we are
Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease
Hb made of fourprotein chains
2 alpha chains2 beta chains
Where we are
Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease
Each Hb moleculehas four Heme groups
Where we are
Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease
Oxygen IS molecular, so TWO oxygen atoms
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
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
You’ve seen this before:Amino Acid sequence
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
How is this determined?
You’ve seen this before:Amino Acid sequenceAlpha Helix
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
You’ve seen this before:Amino Acid sequenceAlpha Helix
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
How is this determined?
You’ve seen this before:Amino Acid sequenceAlpha HelixFolded peptide
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
You’ve seen this before:Amino Acid sequenceAlpha HelixFolded peptide
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
How is this determined?
You’ve seen this before:Amino Acid sequenceAlpha HelixFolded peptideAggregation of peptides
http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology
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Hemoglobin: what is it?
Image source: 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...