W9.1_Secondary Structure of Proteins Flashcards
Why are not all polypeptide conformations possible? How do they avoid misfolding?
- Polypeptide folding is not random -> not all conformations are possible
- Rigid peptide bonds cause limited possibilities in random sequences
- Polypeptide chains adopt specific secondary (2o) structures (further limitations)
- Initiates structure formation within boundaries -> avoid sampling of all random conformation that cause misfolding
Explain the stereoconstraints in secondary protein structures. What are the different secondary structures?
- Angles Φ and ψ controls orientation of two planes per R of backbone
- Stereo-constraints: only certain preferred dihedral angles (Φ/ψ) can result in stable conformations (lie in minimum energy)
- Right-handed helix (common), beta-strands, left-handed helix (very rare)
What is the major driving force in maintaining the stability of secondary structure of proteins? Explain how they are held together.
- Major driving force: hydrogen bond
- N atom attracts e-s around H nucleus -> +ve partial charge -> high charge density at H -> attracts lone pair e-s from O
- Gives rise to secondary structures (regular features)
For right-handed α-helices, describe their structure and how they are held together. Explain what an amphipathic helix is and what it can be used for.
- Repeating Φ=57, ψ=47, stabilised by intra-strand hydrogen bonding
- 3.6 residues per turn
- ∴ CO of each residue is H-bonded to NH of 4th residue
- Twists clockwise (right-handed), peptide bonds are planar, trans R groups extend outside
- Amphipathic helix: helix with hydrophilic and hydrophobic faces
- Can be used to associate a protein/embedded to a membrane
Explain how helices are aggregated through different forces and the variability in helix content.
- Aggregating helices by arranging in membranes with polar forces to centre and non-polar faces towards lipid bilayer (minimum 20 a.a. to span) (ex. transport pore, transmembrane)
- Variable in protein’s helix content (ex. myoglobin/haemoglobin: almost all α-helix, α-chymotrypsin: almost no α-helix)
Describe and explain the structure and functions of keratin, ferritin, and transferrin, which are secondary structures of proteins found in the human body.
- Keratin in hair, myosin in muscle fibres (fibrous structural proteins)
- α-helices wind around each other to form coiled coils -> extremely stable/stiff for support
- Involve S-S bond and other non-covalent interactions to form rigid/strong/insoluble fibre
- ∴ Hair perming needs heat to break S-S bonds and re-form them
- Ferritin: iron storage protein, bundles of helices
intracellular/cytosolic proteins with some in serum - Globular protein (water soluble, 24 subunits with bundle of helices)
- Stores and releases iron as required
- ~4500 Fe3+ ions are caged to reduce toxicity and keeps it soluble
- Important in iron deficiency/overload
- Transferrin: iron transport protein in bloods in ligand, rich in helices
- Each binds 2 Fe3+ ions, delivers to tissues having transferrin receptor 1 (TfR1)
- Binding site has amino acids with electronegative atoms and bidentate carbonate H-bonded to arginine side chain and N-terminus -> stabilise molecules
Explain the special characters and functions of glycine and proline in secondary structure of proteins.
- ∵ Glycine is too flexible, rotation is easy, α-helix loses rigidity
- ∵ proline has a cyclic structure
- ∴ Glycine and proline are mostly found in bends
- ∵ Proline has restricted rotation around (α-N-C due to cyclic structure/fixed Φ)
- ∵ No hydrogen is attached to N atom to form hydrogen bonds
-∴ Proline often serves as α-helix breakers, found at boundaries of α-helices & in turns
Contrast the structures of parallel and anti-parallel beta-sheets.
- Parallel beta-sheet: strands in same direction
- R groups point up/down, H-bonds connect amino acid in one chain with two from another chain
- Strands held by H-bonds between backbone gives ß-sheet
- Anti-parallel beta-sheet: strands run in opposite directions
- R groups point up/down alternately (trans), H-bonds connect amino acids in one chain with one another from another chain
- Could continue another strand to extend the sheet
Describe the sturcture of ß-pleated sheets. Explain how it relates to the structure of silk.
- ß-pleated sheet: side chains alternately up/down, anti-parallel
- Cα tetrahedral, planar peptide bond -> extended structure appear pleated
- R groups lie perpendicular to sheets, stick out on either face
- Both anti-parallel & parallel ß-sheets exist
- Ex. Anti-parallel in silk -(-Gly-Ser-Gly-Ala-Gly-Ala-)-n
- Alternate glycine -> all glycines on one side to give very smooth texture, tightly packed and strongly bonded with regularity
Describe the structure and usual composition of ß-turns. What would happen when misfolded proteins are expressed? Explain how some of the poly-amino acid chains would be affected by pH.
- ß-turns: change directions of sheets/helices, classified into type 1/2
- Often proline (∵ fixed Φ causes a bend) and glycine (∵ very small and flexible side chain -> easy to fit into turns)
- Expression of misfolded proteins -> toxicity to cells -> interfere neurotransmission -> neurodegenerative diseases (ex. Parkinson’s, Alzheimer’s)
- Poly-Lys (only in high pH)/Poly-Asp (only in low pH)/Poly-Glu (only in low pH): charged -> R-groups point out -> repel to destabilise the helix
- Others: zwitterionic in natural form -> unaffected by pH
