1 - Protein Folding and Structure

Question 1

What are trigger factors?

Answer 1

A molecular chaperone that binds to the nascent chain, creating a protective cavity that allows for nascent folding.

Question 2

What is represented by the depth of the trough at any point of a folding funnel?

Answer 2

The overall change in enthalpy.

Question 3

What is represented by the width of the trough at a point on a folding funnel?

Answer 3

The total entropy of the protein component.

Question 4

What processes drive the formation of the protein globule?

Answer 4

Increase in solvent entropy, and to a far lesser extent decrease in solvent enthalpy.

Question 5

What processes resist protein globule formation?

Answer 5

The negligible increase in enthalpy and decrease in entropy of the protein.

Question 6

What thermodynamic forces affect full protein folding from a globule state?

Answer 6

Large decrease in enthalpy of the protein drives secondary/tertiary structure formation. Resisted by a slight decrease in entropy.
There is no change in the thermodynamic properties of the solvent.

Question 7

How does the folding funnel diagram differ between a normally folded protein and an intrinsically disordered one?

Answer 7

IDPs have far shallower funnels with more erratic shapes.

Question 8

What are the two main classes of molecular chaperones?

Answer 8

Class I - Hsp Type Proteins

Class II - Chaperonins

Question 9

What are some examples of Class I chaperones?

Answer 9

Hsp70, Hsp40, DNAK, DNAJ

Question 10

What are some examples of Class II chaperones?

Answer 10

GroEL/GroES

Question 11

What are two molecular chaperones that do not fit into either class I or II?

Answer 11

Protein Disulphide Isomerase (PDI)

Peptide Prolyl Cis-Trans Isomerase (PPI)

Question 12

What enantiomer form do natural amino acids exist in? How is this simply visualised?

Answer 12

L-conformation.Viewing down the Ca-H bond the substituents are so arranged that the acid, R group and amine group can be thought to be spelling CORN.

Question 13

What stereoisomer form does the amide bond exist in almost exclusively?

Answer 13

Trans, to avoid steric clash.

Question 14

Which amino acid is also able to exist in significant amounts of cis-conformation?

Answer 14

Proline, 6-20% are cis. The transitino between the two can be expedited by Peptide Proline Isomerises.

Question 15

What are rotamers?

Answer 15

Different relative rotational conformations of the atoms at either end of a bond, the other substituents of either atom either lining up (eclipsed) or staggered.

Question 16

What determines the relative proportions of rotamers in a chain?

Answer 16

The steric clash between the substituents on connected atoms means that staggered conformation is generally favoured, and determines which of the three ways in which hetero-atoms can be either staggered or eclipsed is most common.

Question 17

How are R group torsion angles denoted?

Answer 17

As a Chi with the atom number noted in superscript.

Question 18

Which amino acid atom is denoted as C-a?

Answer 18

The central one to which the R group is attached.

Question 19

What two bonds allow change in protein conformation by allowing rotation around them?

Answer 19

The C-Ca (Psi) and the Ca-N (Phi) bond, as the amide bond itself has too much double bond character to rotate.

Question 20

What is the sequence of amino acid backbone hydrogen bonding in helices?

Answer 20

Alpha helices - i+4
Overwound (3_10) helices - i+3
Underwound (pi) i+5 also observed but rarely.

Question 21

What does the consistent orientation of the residue backbones in a helix lead to?

Answer 21

A net macroscopic dipole moment along the length of the helix.

Question 22

What is the dipole moment of an amino acid residue?

Answer 22

Each residue has a dipole moment of 3.5 Debye Units.

Question 23

How can the helix dipole moments be calculated?

Answer 23

3.5 debye units x No. of residues in the helix

Question 24

How much charge is produces on each end of a helix due to the net dipole moment?

Answer 24

0.5-0.7e

Question 25

Which end of a helix is positive/negative?

Answer 25

N-terminus = Positive
C-terminus = Negative

Question 26

What are helix termini often used for?

Answer 26

Stabilising molecules of the corresponding charge with their net dipole moment.

Question 27

What structure causes the greatest extension of the polypeptide chain possible?

Answer 27

The beta-strand

Question 28

How are the hydrogen bonds in an antiparallel beta sheet arranged?

Answer 28

Perpendicular to the length of the chain, and parallel to each other.

Question 29

How are the hydrogen bonds in a parallel beta sheet arranged?

Answer 29

At non-perpendicular angles to the length of the chain, alternating between acute and reflex. They are not parallel to each other.

Question 30

How do long beta sheets bind to the next and following strands?

Answer 30

The strands are slanted against each other, leading to an overall right handed twist.

Question 31

What structure does the right handed twist in antiparallel sheets allow for?

Answer 31

Beta helices

Question 32

Describe beta turns.

Answer 32

Often used to link antiparallel beta strands.
Residue 1 carbonyl hydrogen bonds with residue 3 amine.
Often use glycine and proline to support their tight hairpin conformation.

Question 33

What is the first level of tertiary structure classification?

Answer 33

All α, all ß and both α & ß.

Question 34

What types of structures are found within the both α & ß proteins?

Answer 34

TIM Barrels
Sandwiches
Rolls
Anything containing ß-α-ß motifs.

Question 35

What types of structures are found within all α proteins?

Answer 35

EF hands, transmembrane pore bundles.

Question 36

What types of structures are found within all ß proteins?

Answer 36

ß-helices, ß-hairpins, greek key-motifs.

Question 37

How many types of greek key motifs are possible, and how many of these are found in nature?

Answer 37

24 possible combinations identified, only eight found in nature, vast majority just two types.

Question 38

What are Rossman Folds often used for?

Answer 38

Rossman folds often produce clefts in the protein that act as active sites or binding sites for cofactors/ATP.