JW - Protein Architecture Flashcards
What characterizes Amphipathic Helices in terms of hydrophilicity and hydrophobicity?
One side is hydrophilic, and the other is hydrophobic
E.g. caused by every 7th amino acid being hydrophobic
How do Amphipathic Helices behave in water and lipid bilayers?
In water: Hydrophilic outside, hydrophobic inside
In lipid bilayer: Hydrophilic inside, hydrophobic outside.
What is the key feature of Leucine Zippers in terms of amino acid composition?
Every 7 amino acids is a leucine, forming heptad repeats and dimers.
- Traditionally found as transcription factors
How is protein tertiary structure stabilized, and what drives protein folding?
- Stabilized by multiple weak interactions.
- Folding is driven by the hydrophobic effect
List three types of interactions that stabilize protein tertiary structure
- Van der Waals interactions
- Ionic interactions
- Hydrogen bonds
What is present in the interior and exterior of the water soluble protein: Myoglobin?
Interior
- Many hydrophobic residues
Exterior
- Many hydrophylic residues
What is the special property of Cysteine regarding protein structure?
Formation of disulfide bonds, contributing to protein stability
Define quaternary structure and provide an example of a homo-dimer
Polypeptide chains assembling into multi-subunit structures
Example:
- DNA binding protein
- Cro of bacteriophage λ
What are post-translational modifications?
Several different amino acid side chains can be covalently modified to alter protein function
What are 4 features regarding post-translational modifications?
- Typically reversible
- Enzymatically catalysed
- Enhance functional diversity
- Local, temporal control of function
What amino acids are commonly involved in phosphorylation?
Serine (Ser), Threonine (Thr), Tyrosine (Tyr) are commonly phosphorylated
What mediates the catalysis of phosphorylation?
The reaction is naturally very slow.
Hence catalysed by kinases and removed by phosphatases
What structural elements characterize the kinase domain? (3)
- N-lobe predominantly b-sheet
- ATP binding cleft
- C-lobe predominantly a-helix
What states can a protein exist in?
Unfolded state
→ Native (Useful)
→ Disordered aggregate (Unfunctional)
→ Degraded aggregate (May form amyloid fibril) (Not good)
What protein helps other proteins adopt their functions?
Chaperones
How is it shown that 3D structure is encoded in the amino acid sequence?
- Oxidation under denatured conditions leads to the formation of wrong disulfide bonds
- However, renaturation first and then oxidation leads to correct disulfide bonds
=> Amino acid sequence on its own encodes the correct three-dimensional structure of a protein
Describe the progression to the folded state in the Protein Folding Funnel.
Unfolded protein:
- many configurations
- many interactions between residues but few native-like interactions
Transition state:
- many contacts & key residues have native contacts (c.f. yellow spheres)
Native state:
- many interactions, all are native interactions
Native state must have many residue contacts with all of them translating to native interactions
What infectious agent is entirely composed of the protein Prp, and what diseases does it cause?
Prion
Prion causes:
- BSE (mad cow’s disease)
- CJD in humans
- Scrapie in sheep
What is the mechanism of Prp replication? (2)
Normal cellular Prpc spontaneously converts to PrpSc
PrpSc catalyses the accumulation of more misfolded proteins from normal proteins
Differences: Prpc and PrPSc
PrPSc: richer in β-strand
What common feature is associated with protein misfolding in diseases?
Formation of amyloid deposits
- Often characterized by common β-structure in misfolded fibers (amyloid)
