module 2 Flashcards
Describe where you would expect to find polar and non polar amino acids in a folded globular protein
- Polar amino acids are found on the surface of the proteins do to their polar bonds forming H-bonding
- Non polar amino acids are buried in the core
Disulphide bridges are usually found in the core too, due to the forming of a disulphide causing it to lose its polarity!!!
- Non polar amino acids are buried in the core
Describe were you would expect to find Gly and Pro in a folded protein
- GLY is usually found where the polypeptide is turning direction
- because GLY has no side chain and is really flexible and can be accommodated in different turns
PRO is also found where the polypeptide is turning
-because PRO has a sidechain that is fixed onto its backbone (restricted geometry) can only be found in certain placed. PRO is only found in certain structures
List the overall features of folded protein
· Protein folding is cooperative (all or none)
· Transition state between two states: folded or unfolded
· Folded and unfolded states are in equilibrium
Protein folding is reversible
why is protein folding is said to be cooperative
· Generally if any part of a protein is disrupted the interactions with the rest of the protein structure are disrupted and the remainder of the structure will be lost
· Conditions that disrupt any part of the structure will lead to the whole protein unravelling
· Therefore this mid point of folded and unfolded proteins exists in 1/2 fully folded and 1/2 fully unfolded proteins
Explain how Christian Anfinsen’s experiments showed that under appropriate conditions protein folding is reversible
The way you remove the denaturants is important, because the wrong order will not allow the peptide to refold back to its native state
Describe the role of disulphide bonds in protein folding
· Disulphide bonds increase the relative stability of the folded state over the unfolded states/s
Lock on the correct folded state
- Stabilization of Tertiary Structure:
- Form covalent bonds between cysteine residues.
- Act as “staples” holding protein regions together.
Describe how cellular conditions are not ‘ideal’ for protein folding
· Conditions in the cell can make folding slow or impossible
· This is because of molecular crowding
§ Cells are highly concentrated solutions of proteins, nucleic acids, sugars and lipids etc
§ Therefore, inappropriate interactions may occur with other molecules before the protein can fold
Explain how the role of protein folding chaperons in ‘protecting’ unfolding proteins from ‘misfolding’
- Protecting Unfolding Proteins:
- Chaperones assist in proper folding of proteins.
- Bind to unfolding or partially folded proteins.
- Prevent aggregation or misfolding during folding process.
- Preventing Misfolding:
- Guide folding intermediates along correct pathways.
- Shield hydrophobic regions prone to aggregation.
- Facilitate correct folding by providing a favorable environment.
- Quality Control:
- Recognize and target misfolded or damaged proteins.
- Assist in refolding or direct proteins for degradation.
- Maintain cellular proteostasis and prevent accumulation of toxic aggregates.
what do chaperons do
§ Chaperons assist folding by binding to the unfolded/partially folded polypeptides and protect them from misfolding. These bonds are temporally exposed hydrophobic regions preventing them from interacting with the wrong partners (inappropriate interactions)
List the forces that drive protein folding and which chemically groups and amino acids types are involved in each interaction
· Electrostatic forces
· Van der Waals interactions
· Hydrogen bonds
Hydrophobic interactions
explain the thermodynamics basis of the hydrophobic interaction at lower entropy
· At lower entropy the hydrophobic (yellow) are surrounded by water which is not interacting with the hydrophobic side chain, the waters are interacting with eathother and forming a cage around the hydrophobic side chain
There is lots of order around the lower entropy as the waters are joined together
explain the thermodynamics basis of the hydrophobic interaction at higher entropy
At higher entropy (folded protein), the ordered waters are released which increased disorder, thus helping proteins fold!!!!
on a Ramachandran plot, what axis is the psi angle on
y axis
on a Ramachandran plot what axis is the phi angle on
x axis
what are the 4 different regions on a Ramachandran plot
1) Alpha
2) Beta
3) Left handed truns
4) Disallowed
Interpret structural information from a Ramachandran plot
- Top left is where u find beta sheets
- Upper middle right is where you find left handed turns
- Lower middle left is where you find alpha helices
The white area is the disallowed region (not impossible to find but highly uncommon due to steric hinderance
what does a ramachandran plot show A Ramachandran plot
shows the distribution of phi and psi dihedral angles that are found in a protein
describe how hydrogen bonding helps make proteins compact
- The atoms of a hydrogen bond can approach much closer then a VDW interaction (2.7A compared to a 1.9A) due to covalent character of the hydrogen bond
This increased the compactness and stability of a protein
identify different hydrogen bonding interactions on a protein
- Backbone to backbone
- Backbone to side chain
Sidechain to sidechain
- Backbone to side chain
Explain why alpha helices are often ‘amphipathic’
- Alpha helices have both hydrophobic and hydrophilic sections
- In the alpha helix
§ Hydrophobic areas face in
§ Hydrophilic areas face out
‘amphipathic’ means both hydrophobic and hydrophobic
- In the alpha helix
draw a simplified helical wheel diagram
what does a heptad repeat patten highlight
The term “heptad repeat” refers to a repeating pattern of seven amino acids within a protein sequence. Each heptad typically consists of seven positions labeled “a” through “g”, with positions “a” and “d” often occupied by hydrophobic amino acids.
List the structural properties of beta sheets
Parallel or antiparallel
Explain the difference between beta sheets and a beta strand
A beta sheet consists of two or more beta strands. The strand is the element
Explain how a beta sheet can have hydrophilic and hydrophobic face
- Hydrophobic side chains are packed into the core of the barrel
- Hydrophilic side chains are projected outwards into the solvent
§ Stabilized by entropic waters
- Hydrophilic side chains are projected outwards into the solvent
what is the properties of the peptide bond
The peptide bond is usually trans, planar and fairly rigid
why do proteins compact
Proteins are compact because of favourable VDW contacts and hydrogen bonds
what is need to bury hydrophobic residues
There is an entropic requirement to bury hydrophobic residues
what are the 3 common supersecondary structures
- Alpha-alpha hairpin is 2 alpha helices joined together by a turn
- Beta-beta hairpin is 2 beta strands linked together but a turn, these two strands are antiparallel
Beta-alpha-beta is a beta strand, followed by an alpha helix and then a beta strand. This generates 2 beta strands that are paradelle!!
- Beta-beta hairpin is 2 beta strands linked together but a turn, these two strands are antiparallel
what is the link between evolution and proteins
over time as the structure of a protein changes due to the changes in amino acid sequence the structure and function changes. different parts of the protein mutate at different rates
how much of the protein is needed to change before the function of the protein changes function
more the 75% is needed
