Lecture 7: Protein structure and function

Question 1

What are proteins?

Answer 1

Proteins are polymers made up of monomeric subunits called amino acids.

Question 2

What are the functions of proteins?

Answer 2

Proteins regulate growth, metabolism, maturation, digestion, inflammation, movement and reproduction.

Question 3

How do amino acids differ?

Answer 3

Amino acids differ by R groups. Different combination of amino acids form different proteins.

Question 4

How do polar and non-polar amino acids differ?

Answer 4

Polar amino acids have an unequal sharing of electrons in their side chain and are usually hydrophilic. Non-polar amino acids have an equal sharing of electrons in their side chain and are usually hydrophobic.

Question 5

How do essential and non-essential amino acids differ?

Answer 5

Essential amino acids are sourced through the diet whereas non-essential amino acids are formed by our body from the essential amino acids or breakdown of proteins.

Question 6

How are amino acids held together to form polymer chains?

Answer 6

Amino acids are held together by peptide bonds through a condensation reaction to form a covalent bond.

Question 7

What determines amino acid sequence?

Answer 7

Amino acids are joined in a genetically determined sequence.

Question 8

What is the primary structure of proteins?

Answer 8

Long chains of amino acids in a polypeptide chain.

Question 9

What is the secondary structure of proteins?

Answer 9

e 3D form of local segments of proteins. The two most common secondary structural elements are alpha helices and beta sheets.

Question 10

What are alpha-helices?

Answer 10

Interactions whereby hydrogen bonds form between carbonyl groups along the backbone at every 4 amino acids along the chain. 3.6 amino acids per turn.

Question 11

How are alpha-helices formed?

Answer 11

Hydrophilic heads form hydrogen bonds between carbonyl groups and amino groups at every 4 amino acids.

Question 12

What are beta pleated sheets?

Answer 12

Interactions that form a flat structure of laterally packed beta sheets. Side chains are above and below the structure.

Question 13

What are loops and turns?

Answer 13

Secondary protein structure whereby turns occur at roughly every 3-5 AA along forming a sharp bend which redirects the polypeptide backbone

Question 14

What are side-chain interactions?

Answer 14

Side chain interactions involving van der Waals forces, hydrogen bonds and electrostatic forces that alter the secondary and tertiary structure of proteins. Forces are weak but accumulation of these side chain interactions can improve stability.

Question 15

What is the tertiary structure of proteins?

Answer 15

3D protein structure that occurs when secondary structures spontaneously folded into a 3D conformation.

Question 16

What is the coiled coil structure?

Answer 16

Tertiary protein structure whereby 2 or 3 alpha-helices that have wound around each other.
Example: Keratin and collagen

Question 17

How are tertiary protein structures stabilised?

Answer 17

Tertiary protein structures can be stabilised with covalent cross linkages between cysteines to form disulphide bond.

Typically seen in secreted proteins.

Important where proteins may face pH changes.

Question 18

What is the quaternary structure of proteins

Answer 18

Protein structure seen amongst some proteins which associate with each together by hydrophobic interactions to generate higher order structures. Example: Hb

Question 19

Why is protein shape important to function?

Answer 19

Determines whether the protein can interact with other molecules. Charge on surface of protein also effects its shape; proteins interacting need to have complimentary shape and charge.

Question 20

How do post-translational modifications (PTMs) modulate the function of proteins

Answer 20

By altering their activity state, localisation, turnover, and interactions with other proteins.

Question 21

What are 2 examples of post-translational modifications (PTMs)?

Answer 21

• Phosphorylation: addition of phosphate to specific amino acids.
• Glycosylation: addition of carbohydrates to specific sites on proteins.

Question 22

How are chemical denaturation of proteins differ to heat denaturation?

Answer 22

Protein denaturation by solvents disrupt the non-covalent interactions but is reversible. Heat can also denature proteins but this denaturation is irreversible.

Question 23

What are molecular chaperones?

Answer 23

Molecular chaperones are proteins that bind to the partially folded polypeptide chains and assist them in folding.

Question 24

How do molecular chaperones aid protein folding?

Answer 24

Chaperones help to speed up the folding process, prevent protein aggregation, and prevent non-productive intermediates, all without interfering with protein function.

Question 25

What are the 2 types of molecular chaperones?

Answer 25

1. Heat shock proteins

2. Chaperonins

Question 26

How does protein misfolding lead to Alzheimer’s Disease?

Answer 26

Amyloid beta tertiary structure refolds to contain lots of beta sheets which then form aggregates which are toxic.

Question 27

How does protein misfolding lead to Huntington’s Disease?

Answer 27

Gain of function mutation which results in DNA repeats that leads to protein misfolds and aggregates. Aggregates are toxic and lead to neuronal cell death.

Question 28

How does protein misfolding lead to Cystic Fibrosis?

Answer 28

Mutation resulting in deletion of CTT amino acid at 508 in CFTR protein sequence; protein unable to leave ER resulting in impaired chloride transport and mucus build-up.

Question 29

How does protein misfolding lead to CJD?

Answer 29

Genetically inherited prion protein disease which causes proteins to misfold. Abnormal prion proteins propagate and aggregate to form amyloid plaques which are toxic to neurons.