The 3D Structure Of Proteins Flashcards
What are the three ways in which the folding of a polypeptide chain is determined?
- the amino acid sequence
- the molecular structure and properties of the amino acids
- the molecular environment (ligands, cofactors, solvents and salts)
If the amino acid has a carboxylic group (COO-) what group is it in?
Charged or acidic
If the amino acid has an amine group (NH3+) what group is it in?
Charged or basic
If the amino acid has an amine (NH) or carbonyl (C=O) what group is it in?
Polar
If the amino acid has a hydroxyl (OH) what group is it in?
Polar
If the amino acid has a hydrocarbon what group is it in?
Non-polar hydrophobic
How does the polypeptide chain backbone form hydrogen bonds in the secondary structure?
The carboxyl and amine groups are polar
How are the variable side chains in the polypeptide chain usually arranged?
Trans formation
Why does the peptide bond in a polypeptide chain matter?
The delocalised electrons of the N-CO bond makes the bond ridged, with O and H atoms on opposite sides in the same plane
Around which bond is the rotational freedom found in the polypeptide?
The alpha carbon bond
Which amino acid has the most rotational ability and why?
Glycine, as its side group is only a hydrogen
What determines the conformation of the atoms in a polypeptide?
The minimisation of the energetic state
What happens if the delta G of a molecule is negative?
The molecule will spontaneously fold
What is the free energy of conformation affected by?
The environment:
- aqueous or lipid
- other proteins or molecules including salts and their ionic states
- charges in the environment that could induce further conformational changes
How do hydrophobic interactions work?
They’re driven by the minimisation of the chaos formed by being in an aqueous environment
How do covalent/ disulphide bonds form between neighbouring cysteines?
In an oxidative reaction. The SH groups from each cysteine cross link. This usually occurs in distant parts of the primary sequence but adjacent in the 3D structure. Can form intra-chain or inter-chain polypeptide chains
What are the two issues if proteins misfold?
- the function of a misfolded protein is lost or reduced
- misfolded proteins often have the tendency to self-associate and aggregate
What is the protein that misfolded in Huntington’s?
Huntingtin Htt
What is the protein that misfolded in Alzheimer’s?
Amyloid-beta
What is the protein that misfolded in creutzfeldt-Jacob’s disease?
Prion protein
What is the protein that misfolded in Parkinson’s?
Alpha-synuclein
What is the protein that misfolded in AAamyloidosis?
Serum amyloid A
What is the protein that misfolded in type 2 diabetes?
Islet amyloid peptide
What happens in cystic fibrosis?
Misfolded proteins result in cellular processing that leads to their degradation