BBOL- Proteins

Question 1

What types of amino acids are there?

Answer 1

• Charged polar (acidic and basic)
• Uncharged polar (amide, hydroxyl and sulfhydryl groups)
• Non polar

Question 2

Give examples of different protein shapes

Answer 2

• Globular
• Fibrous
• Multiple polypeptides
• Single subunits

Question 3

What is X-ray crystallography?

Answer 3

Crystalline atoms in the protein would cause x-ray beams to diffract in specific ways, helps determine protein structure

Question 4

What are examples of disease that are caused by one amino acid change?

Answer 4

• Sickle cell anaemia

- Cystic fibrosis

Question 5

What are the features of primary protein structure?

Answer 5

• Conformation of the lowest energy
• Changes when other protein interacts with other molecules in the cell
• Proteins can fold on their own, in a living cell require chaperone proteins

Question 6

Why is protein folding constrained?

Answer 6

• Peptide bond is not fully flexible
• Partial double bond- electrons from O migrate to bond between C-N
• Restricted rotation about C-N
• Weak non-covalent bond (H bonds, ionic and van Der Waals attractions)

Question 7

What is the stability of the final shape of the protein determined by?

Answer 7

• Combined strength of many non-covalent bonds

Question 8

Why do proteins fold?

Answer 8

To minimise disruption to hydrogens bonds in water

• Non-polar hydrophobic side chains inside
• Polar hydrophilic side chains outside
• Folding determined by distribution of polar non-polar amino acids in polypeptide

Question 9

Describe the secondary structure of proteins

Answer 9

• Alpa helix or beta sheet
• Hydrogen bonding between N-H and C=O in polypeptide backbone
• Common structures because they don’t depend on amino acid sequence

Question 10

What are protein domains?

Answer 10

• Substructure produced by part of polypeptide that can old independently into a compact stable conformation
• Typically 40-350 amino acids are modular units
• Proteins often contain several different domains

Question 11

Describe domain shuffling in evolution

Answer 11

• Larger proteins have often evolved through combinations of different domains
• Often domains= exons
• Protein binding sites and active sites often found at domain junctions

Question 12

Describe quaternary structure

Answer 12

• Proteins containing more than one polypeptide
• Subunit describes the way subunits are arranged together and nature of their contacts
• Subunits associate by non-covalent interactions similar to those involved in tertiary
  (hydrophobic interaction, H bonds, salt bridges/ion pairs)
• Some complexes involve 1 type of subunit
• Others contain different types of subunit

Question 13

Give types of tertiary structure

Answer 13

• Fibrous proteins (structural, arranged in long strands, insoluble)
• Globular ( polypeptide chains folded into knot, dynamic functions)

Question 14

Describe fibrous proteins

Answer 14

• Simple elongated 3D structure
• Some intracellular (actin/myosin) or fibrin
• Many extracellular (collagen, keratin)
• Extracellular often contain disulphide bridges
  ( formed in ER before cell export, links two cysteine amino acids, can be intra or inter molecular)

Question 15

Describe globular proteins

Answer 15

• Enzymes, hormones, antibodies, transport proteins, binding proteins, membrane proteins

Question 16

Describe membrane proteins

Answer 16

• Often contain alpha helix, short regions of this span lipid membranes
• Hydrophilic peptide backbone is H bonded to itself in a- helix, shielded from hydrophobic lipid by non-polar side chains
• Proteins have many membrane spanning helices

Question 17

Describe the regulation of protein folding

Answer 17

• Usually co-translational (starts from n-terminal as soon as it exits ribosome while c-terminal end of polypeptides is still being synthesised)
• Molecular chaperones (help correct folding, heat shock as activated by heat that could damage folding

Question 18

What are the consequences of incorrect folding?

Answer 18

• Can cause disease
• Exposed hydrophobic regions cause aggregation and precipitation out of solution
• E.g. Alzheimer’s (amyloid plaques)
• E.g. Prion diseases- BSE

Question 19

How is protein transported?

Answer 19

• Synthesised in cytosol but often required in different cellular compartments, gated transport
• Regulated by complexes of proteins forming selective gate, e.g. transport through nuclear pores
• Transmembrane transport, protein translators move proteins across specific membranes, e.g. cytosol to ER or mitochondria
  (relies on signal peptide to direct protein to correct cellular address)
• Vesicular transport, vesicles budding off one compartments and fusing with another, e.g. ER to Golgi

Question 20

Describe localisation signals

Answer 20

• Protein localisation sequences direct proteins to specific organelles
• Can be signal peptides/patches- peptides usually cleaved by signal peptidase after transport
• Patch, amino acids brought together to form signal after folding
• Signal recognition particles guide proteins to correct translocators
• E.g. signal recognition particle guides new proteins to ER

Question 21

Describe post-translational modification

Answer 21

• Some proteins undergo this
• Proteolysis- cleavage into fragments often with different functions- preproinsulin- proinsulin- insulin
• Addition of carb (glycosylation)
• Addition of lipids (myristolisation)
• Phosphorylation, methylation, acetylation etc.