The 3D strucuture of a protein

Question 1

What is the folding of a polypeptide chain determined by?

Answer 1

• Amino acid sequence
• Molecular structure of amino acids and its properties

The molecular environment(solvents and salt)

Question 2

What is the basic amino acid structure?

Answer 2

• Tetrahedral (alpha carbon central)

R chain conferring determined physiochemical properties

Question 3

What type of molecule is an acidic amino acid?

Answer 3

Polar molecule

Question 4

What charge do acidic amino acids have?

Answer 4

Negative charge

Question 5

What do acidic amino acids do?

Answer 5

Donate protons

Question 6

What type of molecule is a basic amino acid?

Answer 6

Polar molecule

Question 7

What charge do basic amino acids have?

Answer 7

Positive charge

Question 8

What do basic amino acids do?

Answer 8

Accept protons

Question 9

What is the charge of a non polar, hydrophobic amino acid?

Answer 9

Neutrally charged as it has a hydrocarbon side chain

Question 10

In polar amino acids, what are the groups attached to the central carbon?

Answer 10

• OH side chains
• Secondary NH groups
Carbonyl C=O side chain

Question 11

What is the peptide bond?

Answer 11

Peptide bond is flat and planar

Question 12

What is found around alpha carbons?

Answer 12

Rotational freedom within the molecule

Question 13

What does rotational freedom allow?

Answer 13

Allows huge variation in the conformation of the peptide chain

Question 14

What does rotational freedom favour?

Answer 14

Favours formation of structural arrangements like alpha helices and beta sheets

Question 15

What is rigidity in amino acids caused by?

Answer 15

Caused by delocalised electrons around region of the peptide bond

Question 16

What does significant delocalisation give?

Answer 16

Significant delocalisation gives the group a partial double bond character

Question 17

Why is glycine a special amino acid in terms of flexibility?

Answer 17

Glycine is a special amino acid in that the R group consists of a single hydrogen which allows greater flexibility of the peptide backbone

Question 18

What is the free energy of a molecule?

Answer 18

G

Question 19

What is delta G?

Answer 19

Change in free energy

Question 20

What does each molecular structure have?

Answer 20

Each molecular structure has a specific energetic state

Question 21

What determines the most favourable conformation?

Answer 21

Minimisation of energetic state determines the most favourable conformation

Question 22

What is free energy of any conformation affected by?

Answer 22

○ Aqueous or lipid membrane
○ Other proteins or molecules including salts and their ionic states
○ Change in environments:
Receptor binding to ligand

Question 23

In terms of strength, what do weak non-covalent bonds have?

Answer 23

Weak non-covalent bonds have 1/20th strength of covalent bonds

Question 24

What do bonds determine?

Answer 24

Determine folding

Question 25

How do disulphide bonds form?

Answer 25

Disulphide form in an oxidative reaction

Question 26

What do SH from each cysteine do in disulphide bonds?

Answer 26

SH groups from each cysteine cross link

Question 27

What happens to function of mis-folded proteins?

Answer 27

Function of mis-folded protein always lost

Question 28

What tendency do mis-folded proteins have and example?

Answer 28

• Often have a tendency to self associate and form aggregates
Eg. Amyloid-beta(Alzheimer’s)

Question 29

What does protein mis-folding result in and lead to?

Answer 29

• Also result in cellular processing that lead to their degradation:
Cystic fibrosis

Question 30

Why can mis-folding occur?

Answer 30

• 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

Question 31

What is observed in Alzheimer’s regarding APP?

Answer 31

Proteolytic cleavage of APP is observed

Question 32

What is APP involved in?

Answer 32

APP is involved in G protein signalling

Question 33

What does a cleavage in APP result in?

Answer 33

Cleavage of APP results in a 40 residue beta amyloid

Question 34

What does the 40 residue beta amyloid do?

Answer 34

Anchors the protein in the membrane

Question 35

What happens to beta amyloid in alzheimer’s?

Answer 35

• 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

Question 36

What is the most common mutation in cystic fibrosis?

Answer 36

Most common mutation is a deletion of phenylalanine at residue 508 of CFTR

Question 37

What does mutation in cystic fibrosis lead to?

Answer 37

Leads to mis-folding of the protein whilst it is still in the ER

Question 38

How is the mis-folded protein recognised and what happens to it?

Answer 38

Recognised by cellular machinery that identifies and processes mis-folded protein

Question 39

What are prions?

Answer 39

Mis-folded proteins which interact with other normal proteins

Question 40

What do prions do through interactions with normal proteins?

Answer 40

Induce mis-folding of the normal protein and polymerisation

Question 41

What do oligomers form?

Answer 41

Form fibrils of mis-folded protein

Question 42

What is the process of prions binding to normal proteins reliant upon?

Answer 42

Process reliant upon the concept of energy minimisation

Question 43

What process is brought about by prions?

Answer 43

Dynamic process brought about by the interaction of molecules resulting in a more stable aggregated structure.