Lecture 5: Protein Folding and Pathologies Flashcards
What must a linear sequence of amino acid residues fold into ?
Native conformation
What does unsuccessful protein folding result in ?
Amorphous aggregation
Why is there a lack of motor function in Parkinsons ?
Aggregation of alpha synuclein
What is hereditary renal amloidosis associated with ?
Variant lysozyme
What is needed for protein to fold properly ?
- Unfolding of ribonuclease A
- Addition of chemical denaturant
- Reducing agent
- Denatured protein
- Reflding of RNase A
What contains all the information required to fold the chain into its native 3D structure ?
The amino acid sequence of the polypeptide chain
What way are the disulphide links in an unfolded state ?
Reduced to yield cys residues
What do we observe en route to native state ?
- Hydrophobic collapse
- Slow reorganisation of side chains to attain native structure
What is the native structure at in terms of energy ?
Global free energy minimum
What is the molten state ?
The kinetic and equilbrium protein folding intermediate for a wide range of problems
What does the protein folding itermediate display in the msec range
Displays conformational fluctuations
What does conformational fluctuations in the msec range prohibit ?
Residue specific studies using X-ray crystallography, NMR or other high resolution techniques
What are the characteristics of the molten globule state ?
- Loss of 3 degree structure
- Retention of second degree structure
- Hydrodynamic radius is expanded by 10%
- Chain topology is native like
How many residues does alpha lactalbumin have ?
123
How many disulphide bridges does alpha lactalbumin have ?
4
