3D structure of protein Flashcards
What does the folding of a protein depend on? [3 marks]
- The amino acid sequence.
- The molecular structure and properties of its amino acids.
- The molecular environment (solvent & salt).
What is the isoelectric point? [1 mark]
The pH value at which a zwitterion has an equal number of positive and negative charge.
What properties do glycine have? [1 mark]
Properties that reduce steric hindrance (slowing of chemical reactions due to steric bulk).
Where is polarity located on polar amino acids? [1 mark]
At either side of the peptide bond.
What is the difference between charge amino acids and polar amino acids? [2 marks]
- They don’t carry the charge in the same way.
- Polar amino acids have a dipole.
What conformation is the variable side chain is? [1 mark]
Trans
Why is the peptide bond ridged? [1 mark]
- The delocalised electrons of the NH3-COOH.
- The O2 and H2 atoms are on opposite sides and lying in the same plane.
What do the delocalised electrons do to the peptide bond? [1 mark]
It causes the bond to act like a double bond and restricts movement.
Where is there rotational freedom on the polypeptide chain? [1 mark]
Around the alpha carbon (it allows a huge variation in the confirmation of the polypeptide chain).
Which bonds allow the polypeptide to fold? [2 marks]
- C-Cα (psi bond)
- Na-Cα (phi bond)
What determines the most favourable arrangement of atoms? [1 mark]
The minimisation of free energy (G).
What is free energy of a confirmation affected by? [3 marks]
- Aqueous or lipid membrane
- Other proteins or molecules (including salts and ionic states)
- Changes in the environment (e.g. a receptor binding a ligand)
What are the non-covalent bonds in proteins? [4 marks]
- Electrostatic attractions
- Hydrogen bonds
- Van der Waals attraction (dipoles)
- Hydrophobic interaction
Where do disulphide bonds occur? [1 mark]
Cysteine
What are the two types of beta sheets/turns? [2 marks]
- Antiparallel: N-terminus of one strand is adjacent to the C-terminus of the next.
- Parallel: N-termini of successive strands are oriented in the same direction.
Which diseases result from misfolded proteins? [6 marks]
- Huntington’s (Huntingtin)
- Alzheimer’s (Amyloid-beta)
- Parkinson’s disease (Alpha-synuclein)
- Type 2 diabetes (Islet amyloid polypeptide)
- PrPSc (Prion proteins)
- AA amyloidosis (Serum amyloid A)
What can mis-folding be caused by? [6 marks]
- Somatic mutations.
- Errors in transcription or translation.
- Failure of the folding machinery.
- Mistakes of the post-translational modification or in trafficking in proteins.
- Structural modification via environmental changes.
- Induction protein mis-folding by seeding and cross seeding by other proteins.
What is seeding? [1 mark]
When a normal protein is exposed to a protein in a disease-causing confirmation and that normal protein becomes mis-folded.
What causes Alzheimer’s? [3 marks]
- Unusual proteolytic cleavage of amyloid precursor protein (APP).
- APP builds up in the cell and turn in beta sheets.
- Amyloid fibrils form and stack up.
What causes cystic fibrosis? [3 marks]
- Deletion of Phe at position 508 of the cystic fibrosis transmembrane conductance regulator (CTFR).
- Protein misfolds while it’s still in the ER.
- Protein gets degradation.
What do prions rely on? [2 marks]
- Relies on minimisation of free energy
- A dynamic process brought about by the interaction of molecules resulting in a more stable aggregated structure.
