1 - Protein Folding and Structure Flashcards
What are trigger factors?
A molecular chaperone that binds to the nascent chain, creating a protective cavity that allows for nascent folding.
What is represented by the depth of the trough at any point of a folding funnel?
The overall change in enthalpy.
What is represented by the width of the trough at a point on a folding funnel?
The total entropy of the protein component.
What processes drive the formation of the protein globule?
Increase in solvent entropy, and to a far lesser extent decrease in solvent enthalpy.
What processes resist protein globule formation?
The negligible increase in enthalpy and decrease in entropy of the protein.
What thermodynamic forces affect full protein folding from a globule state?
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.
How does the folding funnel diagram differ between a normally folded protein and an intrinsically disordered one?
IDPs have far shallower funnels with more erratic shapes.
What are the two main classes of molecular chaperones?
Class I - Hsp Type Proteins
Class II - Chaperonins
What are some examples of Class I chaperones?
Hsp70, Hsp40, DNAK, DNAJ
What are some examples of Class II chaperones?
GroEL/GroES
What are two molecular chaperones that do not fit into either class I or II?
Protein Disulphide Isomerase (PDI)
Peptide Prolyl Cis-Trans Isomerase (PPI)
What enantiomer form do natural amino acids exist in? How is this simply visualised?
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.
What stereoisomer form does the amide bond exist in almost exclusively?
Trans, to avoid steric clash.
Which amino acid is also able to exist in significant amounts of cis-conformation?
Proline, 6-20% are cis. The transitino between the two can be expedited by Peptide Proline Isomerises.
What are rotamers?
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.
What determines the relative proportions of rotamers in a chain?
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.
How are R group torsion angles denoted?
As a Chi with the atom number noted in superscript.
Which amino acid atom is denoted as C-a?
The central one to which the R group is attached.
What two bonds allow change in protein conformation by allowing rotation around them?
The C-Ca (Psi) and the Ca-N (Phi) bond, as the amide bond itself has too much double bond character to rotate.
What is the sequence of amino acid backbone hydrogen bonding in helices?
Alpha helices - i+4
Overwound (3_10) helices - i+3
Underwound (pi) i+5 also observed but rarely.
What does the consistent orientation of the residue backbones in a helix lead to?
A net macroscopic dipole moment along the length of the helix.
What is the dipole moment of an amino acid residue?
Each residue has a dipole moment of 3.5 Debye Units.
How can the helix dipole moments be calculated?
3.5 debye units x No. of residues in the helix
How much charge is produces on each end of a helix due to the net dipole moment?
0.5-0.7e
