Determinants of Protein Structure How Structure dictates Function Flashcards
What is the main determinant of a proteins shape?
The sequence of amino acids
How is the folding of proteins controlled?
By the non-covalent bonds/interactions between amino acids
What interactions drive protein folding in an aqueous environment and how?
Hydrophobic associations drive protein folding in aqueous solution
- Non- polar amino acids chains are repelled by water and cluster together in the centre of a protein
- Clustering of hydrophobic side chains in the centre of the protein allows residues involved in non-covalent interactions to come close enough for these interaction to occur
What non covalent interactions are present in proteins?
- Hydrogen bonds
- Electrostatic attractions
- Van der Waals
What occurs within the secondary structure of a protein?
- Alpha helix
- Intra-strand interactions of amino acid backbone
- Beta sheet
- Inter-strand interactions of amino acid backbone
- alpha helices and beta sheets can form larger secondary structures
- BAR domain –binds to curved membranes
- Beta Barrel –Common in membrane pores
- Hydrogen bonds stabilise structures
How strong are weak interactions?
They can be easily broken apart by thermal motion
Properties of Hydrogen bonds
Formed from the sharing of a hydrogen atom between two electronegative atoms
Properties of ionic bonds
Interactions between oppositely charged groups of a molecule
Properties of Van der waals
Weak attractions or repulsions occurring between atoms at close range
Properties of hydrophobic associations
Hydrophobic amino acids cluster together as a result of their repulsion by the hydrogen bonded water network in which the protein is dissolved. Locate away from molecule surface
How do hydrogen bonds form?
- A hydrogen bond is the electrostatic attraction between polar molecules
- Electronegative atom causes decentralisation of the electron cloud giving H a delta +ve charge
- Lone pair of electrons on oxygen of neighbouring atom has delta -ve charge
- Attraction of lone pair by the positive charge results in a hydrogen bond
- Hydrogen bonds are specific for certain atom types
- Electronegative atoms (N & O).
- Common in proteins
- directional (impart geometry) to drive secondary structure
How do ionic bonds form?
- Some amino acids have side chains containing carboxylic acids groups (e.g. Glutamic acid & Aspartic acid)
- Some amino acids have side chains containing amine groups (e.g. Lysine & Arginine)
- An ionic bond can form between these by transfer of the H from –COOH to the NH2
- In a protein these ionic bonds help to stabilise protein structure
- Because these are ionisable groups, with a defined pKa, the pH of the environment is important for their formation
How do van der waals form?
- The electron cloud around an atom is constantly fluctuating
- These small (delta) charge differences between atoms can give rise to attraction or repulsion between atoms
- Although individually very small, when the sum of all the van der Waals forces in a protein are summed they are significant for maintaining protein structure
What is a proteins quarternary structure and how does it form?
- Multiple protein subunits can combine together to form multimeric proteins
- i) hydrophobic association
- Regions of hydrophobic amino acid side chains on the exterior of a folded protein may form the contact sites for other proteins
- Once the subunits come together the hydrophobic regions are then hidden away from water
- The alpha helices form with a leucine residue at every second turn. These form a hydrophobic region running down one side of the helix
- responsible for proteins that bind at DNA recognition sites
- ii) disulphide bridges
- The oxidation of sulfhydryl groups on the amino acid cysteine gives rise to the formation of a disulphide bridge
- Can undergo reduction and oxidation to form/ break the bonds
- Present in antibodies
What is denaturation and how does it occur?
- factors disrupt protein structure, but do not break the peptide bond and therefore leave primary structure unaffected
- Temperature, pH and various chemicals can disrupt protein folding
- Temperature
- Increased thermal energy disrupts hydrogen bonds and other bonds holding proteins together
- pH
- Changing the pH will affect the charge of the amino acids and cause disruption of ionic bonds
- Salts
- Chaotropicagents such as urea, imidazole and guanidinium disrupt hydrogen bonding and the hydrophobic effect.
- Temperature
