Module 2 Protein structure Flashcards
Describe where you would expect to find polar and nonpolar amino acids in a folded globular protein
Non polar amino acids are hydrophobic so they are in the inside – uncharged. Polar amino acids are the outside, charged hydrophilic
Describe were you would expect to find Gly and Pro in a folded protein.
Glycine located on top of turns – geometrically flexible. Proline is geometrically restricted – less common in turns.
Proline can’t hydrogen bond with no hydrogen present -NH, also has steric hindrance with its bond back. Glycine only has a hydrogen - R groups cannot provide stability
List the overall features of folded proteins.
Overall features
Compact and no water inside the proteins
Explain why protein folding is said to be cooperative.
Cooperative – if one amino acid folds, it is easier for one to fold too
Explain how Christian Anfinsen’s experiments showed that under
appropriate conditions protein folding is reversible.
Christian Anfinsen’s experiment –
Add urea disrupts hydrogen bonding
B-mercap – acts as reducing agent to the disulfide bridges
Remove urea first then B-mercap – shows disulfide bonds rely on hydrogen bonding
Hydrogen bonding direct disulfide bonds
Describe the role of disulfide bonds in protein folding.
Disulfide bonds in proteins → increases stability of folded state over unfolded state
Describe how cellular conditions are not ‘ideal’ for protein folding.
Overcrowding of lipids and nucleic acids → will form inappropriate fold instead of producing correct polypeptide (molecular crowding) - makes protein folding slow
Explain the role of protein folding chaperones in ‘protecting’ unfolded
proteins from ‘misfolding’.
Chaperson hsp70 – binds to hydrophobic regions to prevent misfolding during translation in the ribosome
List the forces drive protein folding and which chemical groups and amino acid type are involved in each interaction.
Hydrogen bonds (weaker than covalent/ionic) – Interaction of N-H and C=O form a/b helix and sheets, required hydrogen bond donor, acceptor which comes from dipole. Most favourable collinear position.
Weak van der waals (weak) – weak electrostatic forces temporarily with electron rich/poor areas - dipole → many = increase protein stability - favourable distance
Electrostatic interactions (strong) – permanently charged groups, Basic/Acidic (Arginine/Glutamine), form salt bridges which stabilise the protein in hydrophobic environments
Dipoles – partial double bond due to resonance → electronegativity alternate to having ‘charges’
Hydrophobic effect - releasing water molecules from solvent layer increase net entropy - between water molecules and non polar molecule (folded polypeptide = increase entropy and increase stability), relies on C-H having similar electronegativity (unable to H-bond)
List the different regions of a Ramachandran plot.
Ramachandran plot - top left is B sheets, bottom a-helix, right L turns, Disallowed on the bottom
All for L-amino acids (naturally occurring ones) Note the positive phi angles become less favourable to structures
dentify different hydrogen bonding interactions in a protein
Hydrogen bonds can occur between backbones, backbones to sidechains, and side chains to each other - a-helix have internal hydrogen bonds between i and i-4 residues
Describe how hydrogen bonding helps make proteins compact.
Hydrogen bonds are present in every polar group – has a smaller distance compared to VDW and increases stability and compactness
- List the structural properties of alpha-helices.
Alpha helices - 0.54nm long per turn, 3.6 residues per 100 degrees, heptad repeat with hydrophilic/hydrophobic face, amphipathic
Explain why alpha-helices are often ‘amphipathic’.
Amphipathic means the burying of hydrophobic side by packing two a helix together/a+b sheet
Why certain amino acids affects the helix structure:
Proline = lacks H donor, Glycine = tiny R group lack of stability
Explain the difference between a beta-strand and a beta-sheet.
Beta strands make up beta sheets, sheets held by hydrogen bonds
List the structural properties of beta-sheets.
Antiparallel, parallel, but antiparallel is preferred because H-bonds are more stable. Alternate polar, non polar amino acids
Explain how a beta-sheet can have hydrophilic and hydrophobic face.
Because of the side chains
List the structural properties of reverse turns.
Accomplished over 4 amino acids, stabilised by single hydrogen bond with i/i+3, Proline often in position i+1
Explain the difference between type-I and type-II turns.
Proline in position 2 Type I with R group facing into the page, glycine in position 3 Type II with R group facing out of the page
Define regular and irregular structures.
Irregular structure have no repeating pattern - random coil/loop/B turns. Regular structure stabilised with hydrogen bonds to have repeating pattern of side chains
List the structural properties of proteins.
Trans,planar and rigid peptide bond, repeating phi and psi angles in a-helix and b-strands, buried polar groups form hydrogen bonds, compact, hydrophobic interactions needing entropy, supersecondary structures
Describe the three common supersecondary structures.
Three most common - aa-hairpin, BB-hairpin, BaB - ⅔ proteins have supersecondary
Explain the difference between primary, secondary, tertiary and quaternary
protein structure
Primary: amino acid sequence
Secondary: Alpha helix, B sheets, B turns
(intermediate Sec/Ter) Supersecondary: aa hairpin, BB hairpin, BaB
Tertiary structure: domains, fold, modules (single chain)
Domains may make up one polypeptide (tertiary structure)
Quaternary structure: more than one subunits form large cluster (many chains)
Describes the subunit arrangement
Explain the difference between the terms domain fold and module
Domain: region of tertiary structure of a single strand that folds independently
Fold: arrangement of secondary structure (alpha helix/beta sheets) in space or a single strand
Module: protein domains repeating fold
Define domain in terms of structure and evolution.
Protein domains align based on making a sequence have similar residue line up, evolved through gene duplication/shuffling from a common ancestor
Describe the genetic processes that create proteins with different functional
properties using existing domain structures.
New functional properties used by intragenic mutation, gene duplication, DNA segment shuffles and gene lateral transfer
Explain what is meant by the statement that protein sequences can be
optimally aligned.
Gaps are introduced in the sequence to allow similar residues to align which allows comparison of function of protein in different species
Explain the link between sequence identity, ancestry, and structural similarity
Structural similarity can be observed through either identical residues, which are exactly the same, or similar residues which are residues that have similar properties
Define homologue, orthologue and paralogue
If a protein has >25% similarity, they will have similar structure
Homologue - >25% identity the common ancestor arised from gene duplication
Orthologue: homologous proteins perform same function, different species
Paralogue: homologous proteins perform different burelated function within single organism
