The 3D strucuture of a protein Flashcards
What is the folding of a polypeptide chain determined by?
- Amino acid sequence
- Molecular structure of amino acids and its properties
The molecular environment(solvents and salt)
What is the basic amino acid structure?
• Tetrahedral (alpha carbon central)
R chain conferring determined physiochemical properties
What type of molecule is an acidic amino acid?
Polar molecule
What charge do acidic amino acids have?
Negative charge
What do acidic amino acids do?
Donate protons
What type of molecule is a basic amino acid?
Polar molecule
What charge do basic amino acids have?
Positive charge
What do basic amino acids do?
Accept protons
What is the charge of a non polar, hydrophobic amino acid?
Neutrally charged as it has a hydrocarbon side chain
In polar amino acids, what are the groups attached to the central carbon?
• OH side chains
• Secondary NH groups
Carbonyl C=O side chain
What is the peptide bond?
Peptide bond is flat and planar
What is found around alpha carbons?
Rotational freedom within the molecule
What does rotational freedom allow?
Allows huge variation in the conformation of the peptide chain
What does rotational freedom favour?
Favours formation of structural arrangements like alpha helices and beta sheets
What is rigidity in amino acids caused by?
Caused by delocalised electrons around region of the peptide bond
What does significant delocalisation give?
Significant delocalisation gives the group a partial double bond character
Why is glycine a special amino acid in terms of flexibility?
Glycine is a special amino acid in that the R group consists of a single hydrogen which allows greater flexibility of the peptide backbone
What is the free energy of a molecule?
G
What is delta G?
Change in free energy
What does each molecular structure have?
Each molecular structure has a specific energetic state
What determines the most favourable conformation?
Minimisation of energetic state determines the most favourable conformation
What is free energy of any conformation affected by?
○ Aqueous or lipid membrane
○ Other proteins or molecules including salts and their ionic states
○ Change in environments:
Receptor binding to ligand
In terms of strength, what do weak non-covalent bonds have?
Weak non-covalent bonds have 1/20th strength of covalent bonds
What do bonds determine?
Determine folding
How do disulphide bonds form?
Disulphide form in an oxidative reaction
What do SH from each cysteine do in disulphide bonds?
SH groups from each cysteine cross link
What happens to function of mis-folded proteins?
Function of mis-folded protein always lost
What tendency do mis-folded proteins have and example?
• Often have a tendency to self associate and form aggregates
Eg. Amyloid-beta(Alzheimer’s)
What does protein mis-folding result in and lead to?
• Also result in cellular processing that lead to their degradation:
Cystic fibrosis
Why can mis-folding occur?
• Somatic mutation
• Errors in transcription and translation
• Failure of the folding machinery
• Mistakes in post translational modification
• Structural modification
Proteins cross-seeding and seeding by other protein
What is observed in Alzheimer’s regarding APP?
Proteolytic cleavage of APP is observed
What is APP involved in?
APP is involved in G protein signalling
What does a cleavage in APP result in?
Cleavage of APP results in a 40 residue beta amyloid
What does the 40 residue beta amyloid do?
Anchors the protein in the membrane
What happens to beta amyloid in alzheimer’s?
• Beta amyloid accumulates
○ Mis-folding results in a planar arrangement and polymerisation
○ Can form amyloid fibrils
○ Beta amyloid fibres are formed from stacked beta sheets in which the side chains interdigitate
What is the most common mutation in cystic fibrosis?
Most common mutation is a deletion of phenylalanine at residue 508 of CFTR
What does mutation in cystic fibrosis lead to?
Leads to mis-folding of the protein whilst it is still in the ER
How is the mis-folded protein recognised and what happens to it?
Recognised by cellular machinery that identifies and processes mis-folded protein
What are prions?
Mis-folded proteins which interact with other normal proteins
What do prions do through interactions with normal proteins?
Induce mis-folding of the normal protein and polymerisation
What do oligomers form?
Form fibrils of mis-folded protein
What is the process of prions binding to normal proteins reliant upon?
Process reliant upon the concept of energy minimisation
What process is brought about by prions?
Dynamic process brought about by the interaction of molecules resulting in a more stable aggregated structure.
