Protein Folding Flashcards
What is the primary process that proteins undergo after ribosomal synthesis?
Proteins will spontaneously adopt a well-defined 3D structure
This process is known as protein folding.
What does the energy landscape represent in protein folding?
The energy landscape shows free energy associated with the number of contacts/interactions in different conformational states
It illustrates how proteins fold into their native structures.
What types of contacts influence protein folding?
Native and non-native contacts
Native contacts decrease free energy, while non-native contacts do not.
Native contacts are typically stable and well-defined, and they play a key role in maintaining the protein’s structure and function.
Non-native contacts are interactions that are not present in the native state but may occur in the unfolded or partially folded states.
These contacts are typically transient or unstable and can lead to misfolding or aggregation of proteins.
What is the driving force behind protein folding?
The protein must make only native contacts to reach minimal possible free energy
This allows the protein to adopt its native structure.
What are the potential benefits of understanding protein folding?
- Predict 3D structure of proteins from primary sequence
- Understand and combat misfolding related to human diseases
- Design proteins with novel functions
These applications can have significant implications in biotechnology and medicine.
What was the first step in Anfinsen’s experiment with ribonuclease?
Take ribonuclease and denature it with 8M urea and ß-mercaptoethanol (BME)
This unfolds the protein to a random coil state.
What happens after removing BME and urea in Anfinsen’s experiment?
Non-native disulfide bonds form, and no enzymatic activity is observed
The protein has not yet folded into its native state.
What is the purpose of adding a trace amount of BME in the experiment?
To denature non-native disulfide bonds
This allows the protein to recover enzymatic activity by reforming native disulfide bonds.
Fill in the blank: All information required to reach native structure is coded in the _______.
primary amino acid sequence
This conclusion is a key finding from Anfinsen’s experiment.
What are Intrinsically Disordered Proteins?
Proteins that have sequences preventing hydrophobic forces from driving folding
They make up ~30% of the total proteins in eukaryotic genomes.
What percentage of eukaryotic proteins are intrinsically disordered?
~30%
This indicates a significant presence in the proteome.
What is the relation between intrinsically disordered proteins and diseases?
Some are related to neurodegenerative diseases
Examples include Alzheimer’s and Parkinson’s diseases.
What defines protein stability in terms of folding?
Conformational stability given by the difference in G between denatured (D) and native (N) states
This is different from chemical stability.
What does chemical stability refer to?
The integrity of covalent bonds in the native state
It involves maintaining intact chemical bonds, oxidation states, and metal coordination.
What are disulfide bonds considered in terms of stability?
Borderline between chemical and conformational stability
Breaking covalent bonds can lead to changes in conformation.
Name one process that introduces chemical instability in proteins.
Deamination of Asn and GIn residues
This process converts them to Asp and Glu.
What happens to Asp residues at low pH?
Hydrolysis of the peptide bond occurs
This can lead to destabilization of the protein structure.
What is the effect of high temperatures on Methionine?
Oxidation to methionine sulfoxide
This can affect protein stability.
What does the elimination of disulfide bonds indicate?
Potential chemical instability
This can lead to loss of structural integrity.
What type of modifications can signal protein aging?
Deamination, hydrolysis, oxidation, and elimination of disulfide bonds
These modifications can be observed to track the age of proteins.
What is the relationship between structure and function in proteins?
Structure determines function
This principle is fundamental in biochemistry.
What is the significance of the native state of a protein?
It is more stable (lower G) than the denatured state
Stability influences protein functionality.
What are some diseases associated with intrinsically disordered proteins
What is conformation stability in proteins?
Protein’s ability to adopt/maintain well-defined conformation rather than a random coil.
Refers only to the formation of non-covalent bonds needed to achieve secondary/tertiary structures (hydrophobic interactions/VdW).