Topic 1 - Module 2 Flashcards
(37 cards)
Where are polar and nonpolar side chains generally located in a protein core?
Polar side chains are typically left exposed on the surface, and nonpolar side chains are buried within the protein core.
What is a “turn”?
Hint: how does it assist in describing a globular protein structure?
Describes how a protein is being folded over itself (peptide chain).
More conformational freedom will enable the residue to be located towards the top/surface of the shape.
What molecule is typically excluded from the interior of protein shapes, and why?
Water, due to non-polar chains being buried within the core.
Which protein state is more favorable and why? Explain the result of this change in protein conformation.
the folded state, due to the native state being more stable than its unfolded state.
As such, in solution, the unfolded state will spontaneously fold up, with exposed polar side chains that will form hydrogen bonds with water.
What changes can be made for a protein to transition from its folded state into its native state?
Changes can be made to its pH level, temperature of solution and concentration of the denaturant.
What are the conditions required for protein folding to occur? Provide one example of how correct protein folding can be achieved.
Cooperativity must be reached (under the all or none rule)
Where one part unraveling will lead to the remainder of the structure unraveling; recall that there can’t be half of the protein folded, and rest unfolded or vice versa.
Only the correct pairing of side chains will stabilise the structure (i.e disulphide bonds)
What is the denaturant used for?
Most useful for facilitating the oxidation/reduction (conditions) of protein unfolding and return it into its native form. Hence, under appropriate conditions protein folding/unfolding is reversible.
Explain the main role of chaperones.
Chaperones prevent proteins from misfolding by temporarily binding to exposed hydrophobic regions of a peptide, which stops them from interacting with the wrong substrates. They don’t help proteins to fold up.
Describe how cellular conditions are not ideal for protein folding/unfolding.
molecular crowding (high concentration of cellular contents) is likely to result in proteins misfolding. Moreover, nascent polypeptides are usually exposed to a variety of environments in the cell, and may misfold when detaching from the ribosome.
Describe the entropy of water that the protein is dissolved in during protein folding.
the entropy of the water will increase
A protein that has two domains is most likely to also have: (two hydrophobic cores, two distinct polypeptide chains, one beta-domain and one alpha-domain)
two hydrophobic cores.
What is the thermodynamic basis of hydrophobic interactions?
The removal of hydrophobic side chains causes the release of ‘ordered’ water. This increases the entropy of water, making the reaction (protein folding) to be spontaneous.
How are new proteins with new functions made? Provide examples of these mechanisms.
Generally, they are made by mixing domains and mutating existing domains, in this sense, no protein is entirely created.
Examples: intragenic mutation, gene duplication, DNA segment shuffling, gene lateral transfer.
What is intragenic mutation?
mutations such as point mutation, insertions and deletions.
What is gene duplication? How is gene duplication associated with creating new proteins with new functions?
Genes are duplicated and may be slightly modified when the second copy of a gene is inserted into another gene, giving rise to a new protein with new functions over time
How does DNA segment shuffling relate to creating new proteins with new functions?
Occurs when two or more existing genes are broken and recombined, producing different segments that result in a new protein.
Note: each broken fragment is a domain (or string of domains)
What is gene lateral transfer? Provide an example.
When one organism acquires parts of the genome or another.
Example: viral DNA transfer (viruses inserting their DNA into host cells)
Define a protein domain.
a region within the tertiary structure which can be folded independently to the rest of the polypeptide.
Defined also as an evolutionary unit, with a common ancestor, rather than a structural unit. Due to mutations, will give rise to gain/loss/change of protein function.
On what basis are protein sequences aligned?
Their respective identity and similarity
Define “identity” of protein sequences
The identity of a protein sequence refers to invariants, the parts of sequences that are exactly the same.
Define “similarity” of protein sequences. Provide examples using AA residues to support your answer.
refers to the frequently observed changes in residue or similarities in chemical properties.
Leucine and Valine are differed by one methyl group, yet exhibit similar chemical properties despite obvious structural differences.
Serine and Threonine are both hydroxyls yet do differ by one methyl group.
Based upon ‘identity’, how is the overall protein structure similarity defined?
two proteins with sequences that show >25% identity will result in minor changes in overall protein structure, and hence, can share similar structures.
This is because the structure of proteins changes much more slowly than the sequence.
When are proteins described as homologues? What are the two groups of homologues?
When 2 protein sequences exhibit >25% identity, the protein domains will be labelled as homologues (share common ancestor, and same protein fold)
There are orthologue and paralogue within this category.
What are homologue, orthologues? provide an example.
homologous proteins that perform the same function in different species.
e.g trypsin in horses and in tuna.
