BMS3021 Lecture Notes - Lecture 13: Atomic-Force Microscopy, Surface Tension, Thermodynamics
30 May 2018
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Week 5. Mechanisms of protein folding and
aggregation
MECHANISMS OF PROTEIN FOLDING AND AGGREGATION
• Unfolded proteins are dangerous: hydrophobic groups are exposed which is in danger of
interacting with other partial folded proteins -> can get proteins sequestered into disordered
aggregates
• Protein folding is a reversible process
• Proteins can be inadvertently cleaved
• Fibril formation gives a number of different species
• Intermediate proteins can turn into prefibular species where it forms beta sheets with other
proteins and form long sheet fibres -> amyloid fibril (not much tendency for reversal)
• Afise’s expeiet ith RNase:
o When protein is denatured and urea is added, protein goes into an inactive unfolded
state however when urea and marcaptoethanol are removed, protein automatically
refolds without assistance and goes into an active state again
o Primary sequence of aa contains all the information required to fold the chain into its
native 3D state
o We can predict the structure of a protein from its aa sequence
find more resources at oneclass.com
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Document Summary
Thioflavin t interacts with beta sheet structures. Ft-ir infrared can give information on secondary structures: some organisms have been found to convert during their life cycle one or more of their endogenous proteins into amyloid fibrils that have functional rather than disease properties. E. coli use curlin to colonise surfaces and bind to host protein. Hydrophobin in fungi used to lower surface tension: amyloids are strong, irreversible and water resistant. Inclusions -> oligomers start to stack up -> amyloid fibril (fibrils start to curve) -> deposit: structure: X-ray fibre diffraction indicates cross beta structure. High beta sheet content (cd and ft-ir) Core consists of all residues or as little as 13% of the residues. Whole p(cid:396)otei(cid:374) does(cid:374)"t ha(cid:448)e to tu(cid:396)(cid:374) i(cid:374)to (cid:271)eta sheets. Sequence dictates length, parallel vs antiparallel and length of loops and turns: toxicity: Structures that form early in aggregation are toxic to cells.
