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Ooopsies & Schedule
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I posted Periodic Table w/ ‘normal’ deadline instead of
intended of 9-12 @ 10 p.m.
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Kudos to all of you who did it by the posted deadline!!
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But for the sake of fairness, deadline now 9-16
Next round: Read paper this weekend
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Assessor on Monday/due Thurs p.m.
Quiz custodiet ipsos
custodes?
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Who builds the builder?
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Machines are 3D ‘folded’* strings of amino acids: ‘proteins’
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What forms (folds) the machines out of strings?
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Does anybody see a problem with such a solution?
*Folding is the correct term for an amino acid string being brought into correct 3D
shape
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What do to with my
string of blobs?
Beads on a string
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It is plausible that a string of distinct, shaped ‘feels’
would self-assemble: Prof. Nowicki’s example
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Potential example of amino acid ‘beads’ on a protein
‘string’ shown
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http://sun.menloschool.org/~dspence/biology/chapter3/chapt3_13.ht
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Say hello to a special friend
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Next week in lab, you’ll revel in the glory of histidine
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Today’s special pal: cysteine (recall from Easter Egg
Hunt)
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Concept: the 20 amino acids are a collections of
generalist pieces & specialists with unique capabilities!
Sulfur + Sulfur =
SulfurSulfur
oxidize
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On the importance of bonding ‘H’
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On the importance of bonding ‘H’
(+)
(-)
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alpha helix
Details, details
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One, two, three, four
Steps in assembling a Big Machine
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Great experiments
Boiling an egg, writ small:
Scrambled ribonuclease
The argument
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It is plausible that a string of distinct, shaped ‘feels’
would self-assemble
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alpha-helices, beta-sheets can be drawn; pairings
postulated
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That’s different from evidence
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How beads organize a string:
http://sun.menloschool.org/~dspence/biology/chapter3/chapt3_13.ht
ml
What it is, is...
http://upload.wikimedia.org/wikipedia/commons/c/c0/Ribonuclease_A_7rsa.png
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Ribonuclease the right way
Cartoon of previous
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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.g
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What they then knew
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‘it cuts up RNA’ *
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we can tell if RNA intact vs. cut
up
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(heat drives proteins wild)
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(so do some chemicals--like
urea. From the name, guess
where we can find that?)
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*nomenclature moment: ‘enzyme’ = hastener
protein that does this: -ase
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Like & unlike an egg
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Break disulfide (Cys-Cys through
their sulfurs)
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‘Denature’ (unfold)
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Cool fast
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freezes current state
allow disulfides to reform
It ‘locks in’ to inactive states
Biochemstry, 5th ed.
Berg, Tymoczko & Stryer
Like & unlike an egg
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Disconnect the disulfides
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Allow to re-discover its ‘comfy’
shape (re-fold on its own)
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Allow disulfides to re-lock
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Function!
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Biochemstry, 5th ed. Berg, Tymoczko &
Finding yourself… protein
style
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What’s going on in
there?
Techniques for seeing that which cannot be seen
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From the lab
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By detection of different smells, you deduced
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The presence of molecules
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Their flightiness
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Their structural distinctness
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Your possession of receptors & pathways
An important idea
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To understand a paper, you don’t necessarily need to
understand every component
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If I tell you that…
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amount of habooxiebooble directly reflects the number
of hydrophobic residues in a protein
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Protein A has a greater habooxiebooble than Protein B
What can you tell me?
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How can we know the
shape of a protein?
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X-ray crystallography: the ultimate in (frozen) truth
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Circular dichroism (rotation of polarized light)
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All you need to know: it happens, and it happens
different for different shapes [conformations] of same
1˚ sequence
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Cysteine locking
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Tyrosine wiggling
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Prions: protein folding
diseases
Giving a protein a choice isn’t always a good idea
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What is life?
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Replicates
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Instructs
Mystery diagnosis
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Diseases with LOOOONG onset times--years or decade+
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Infectious particles resistant to UV treatments that blow
DNA, RNA out of the water
Kuru is an incurable degenerative neurological disorder (brain
disease) that is a type of transmissible spongiform encephalopathy,
caused by a prion found in humans.[1] The term "kuru" derives from
the Fore word "kuria/guria", 'to shake'.[2], a reference to the body
tremors that are a classic symptom of the disease; it is also known
among the Fore as the laughing sickness due to the pathologic
bursts of laughter people would display when afflicted with the
disease. It is now widely accepted that Kuru was transmitted among
members of the Fore tribe of Papua New Guinea via cannibalism.[3]
http://en.wikipedia.org/wiki/Kuru_(disease)
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What’s a ‘prion’?
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Alas ‘ protein infectious particle’
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!?! How can this be?
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I will later argue that genetic material must be ‘base like’
with rigid presentation of binary information
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Proteins do not qualify! How can they direct reproduction?
We may talk viruses & such much later, but this is
specifically a protein folding issue, so it’s here
Deadly alternatives
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The secret: conversion of preexisting material to the dark side;
not de novo creation
Still, this very much blurs the
distinction about which structures
can & cannot instruct
Shown is a small section of a much larger protein--but this is the source of the trouble
Biologic Science, Scott Freeman, Fig. 3.15
But wait! There’s more...
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Note that besides the bonds between the two, each offers
donors & acceptors to the outside
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Imagine this going on and on and on...
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One ‘prionized’ protein converts another, and they
convert others...
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Prion diseases: FYI
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http://www.cdc.gov/ncidod/dvrd/prions/
Homework
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Assessor drops on
Mon.
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I challenge you to read
on your own 1st
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