L3: Determinants of Protein Structure Flashcards
What sort of shapes and sizes can proteins come in?
Globular, linear, porous, associated with other molecules etc
Why can protein shape differ?
All different proteins have different functions to carry out in a cell - need to interact with different things, so shape varies to fit a specific function
What is an example of two common, but different environments a protein may need to work within?
- Intracellular = primarily aqueous but has different proteins, salts, etc
- Extracellular = salts and other molecules different to the ones intracellularly
Name 3 examples of where specificity of function is related to shape
- Receptor-ligand interaction
- Antibody-antigen interaction
- Enzyme-substrate interaction
What determines the shape of a protein?
- The sequence of amino acids is the main determinant of a protein’s shape - encoded within the nucleic acid
- This is driven by the DNA and the gene the protein sequence comes from
What are the levels of protein structure?
What characteristic is determined by the Levinthal Paradox?
- Proteins must always fold in ‘pre-arranged’ pathways and in a cooperative manner
- Must be limitation in folding geometry and hydrophobic interactions
- Otherwise a limitless number of potential folding possibilities
What restricts the shapes that can form from an amino acid structure?
- The chemical properties of the atoms and the peptide bond restricts the number of possible shapes
- Non-covalent bonds/interactions between amino acid side chains constrain the folding of the protein
How do hydrophobic associations drive protein folding?
- Non-polar (hydrophobic) amino acid side chain are repelled by water and cluster together in the centre of a protein
- The polar (hydrophilic) amino acids conform on the outside of the non-polar centre - attracted to water
- H bonds form between the polar side chain on the outside of the molecule
- Hydrophobic interactions drive (spontaneous) folding of proteins in aqueous environment
How does clustering of the hydrophobic side chains drive further interactions and folding?
Clustering of hydrophobic side chains in the centre of the protein allows residues involved in non-covalent and covalent interactions to come close enough for these interaction to occur (between amino acid side chains)
What are the two types of secondary protein folding?
- Alpha helix
- Beta pleated sheet
Describe the structure of the alpha helix
- Folding pattern resulting in a helical shape
- Hydrophilic side chains on the outside and available to interact with water with hydrophobic in the centre
- Stabilised by interactions between molecules close enough to form a bond e.g. H bonding
- Intra-strand interactions of amino acid backbone
Describe the structure of beta pleated sheet
- Folding pattern resulting in a kinked sheet structure
- Hydrophilic side chains on the outside and available to interact with water with hydrophobic in the centre
- Stabilised by interactions between molecules close enough to form a bond e.g. H bonding
- Inter-strand interactions of amino acid backbone
What structure can form from the association of many alpha-helices?
- BAR domains
- Binds to curved membranes
What structure can form from the association of many beta-sheets?
- Beta-barrels
- Often associated with membranes and insertion into membranes
What are the 4 types of non-covalent interaction?
- H bonding
- Ionic bonding
- Van der Waals interactions
- Hydrophobic interactions
What is a H bond?
A hydrogen bond is the electrostatic attraction between two adjacent polar molecules
- Directional (impart geometry ) to drive secondary structure
Which two elements can form hydrogen bonding? Why?
-Nitrogen and oxygen
- More electronegative than hydrogen so the electron cloud is shifted slightly more towards the N or O than H (decentralisation of the electron cloud)
- Forms a slight positive charge on H and a slight negative charge on N or O
- Means the slight positive charge on the H is attracted to the lone pair on the N or O
Why do lots of H bonds form between amino acids in protein folding?
High volume of N and O in amino acids - perfect for H bonding
What is an ionic bond?
Electrostatic attraction between a metal and non-metal, formed from the transfer of electrons, to form a giant ionic lattice structure
How do the ionic bonds form in protein folding?
- 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 negatively charged carboxylic acid (COOH) and the positively charged amine group (NH2)
- Forms an electrostatic attraction
- Ionic bonds stabilise the structure
What is important to remember about groups involved in ionic bonding?
Because these are ionisable groups, with a defined pKa, the pH of the environment is important for their formation
What are Van der Waal interactions?
- Electron cloud around an atom is constantly fluctuating
- Means a fluctuation in the charge distribution around an atom (both positive and negative charges)
- These small/slight charge difference between atoms gives rise to attraction or repulsion between atoms
- Weak intermolecular forces on their own, but when combined these form a strong electrostatic attraction which helps maintain and stabilise protein structure
What can hydrophobic interactions allow the formation of?
- Multiple protein subunits can combine together to form multimeric proteins
- 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 protected from the cytosolic regions
