Notes 20100423 Meiering Group Meeting
From SnOwy - Ed's Wiki Notebook
This lab meeting is the first one that this lab has seen in roughly a semester, so Liz has decided to give a presentation on two topics.
Contents |
House Keeping
- unplug everything since the power is being cycled this weekend
- Biochemistry & Beer next Thursday @ 4:30
Crystallography, Amyloids
- David Eisenberg
- 1979 text book
- ribonuclease A -- protein folding model
- created a mutant that creates a domain swapped dimer
- a buried domain is exposed instead after the mutation
- amyloid-like
- causes stacking -- stacked domain swapped dimers => amyloid-like
- domain-swapped zipper-spine model
- perfect steric complementarity
- ordered structure
- the buried region is called a linker region
Amyloid
- this word is controversial-- is it a bunch of strands or is it any domain-swapping zipper-like or chain-like item?
Serpin
- Serine protease inhibitors (Serpins) are another kind of domain swapping disease (amyloid-like)
- depending on the number of betastrands present in a structurally important sheet, the propensity of domains swapping changes
- produces a chain-like structure
Disease Proteins, Steric Zippers
- fibrils
- crystallography generally can't be used for fibrils, but it works for these
- using small peptides now
- needle-like crystals
- no water is used-- complete packing--
- eight possible classes of zippers
- parallel/anti-parallel (2)
- up-up/up-down (2)
- face-to-face/face-to-back (2)
- 2^3 = 8
- of these, five have been observed
- stability: hydrogen bonding, complimentary
- demonstrated that this can be done with any peptide at all
Amyloid-like Structures, Inclusion Bodies
- congo red (?) is used to detect ordered structures
- profile-based methods used
- amylome --
- impossible to say given a native structure what will become the amyloid
- given the proteome, 70% of the sequences have segments that can produce amyloids
- beta strands are heavily implicated, but helical regions can do this too
- test tube sequences produced, testing prediction capability
- notice-- Rosetta binding energy used (given as a per residue number, kcal / mol)
Profile-Based Method
- given a polypeptide stretch, build a peptide-structure map; classify new sequences using the map
Oligomers instead of Fibrils
- doesn't always make a fiber
- example: dimer (penta-domain-swapped-dimers)
More Reading
- Inclusion bodies -- details
- inclusion bodies were previously thought to be noisy, amorphous
- they are actually ordered
- amorphous appearing bodies may be in phase transition
Tau Protein? Another Alpha-Protein?
- bucking the trend that amyloids require beta strands to form
amyloid SOD
- ?
