Session 2 ILO's - Protein structure Flashcards
Identify the structure of a peptide bond
- A peptide bond is formed by 2 amino acids being joined together
- The link is between the carboxylic acid of one amino acid and the amine of another amino acid (involves extraction of water).
- Peptide bonds are also planar (all lie in the same plane)
Identify the properties of a peptide bond
1) Peptide bonds are planar (all lie in the same plane)
2) Peptide bonds are rigid and the C-N bond has partial double bond characteristics
(We can get delocalisation of electrons which means the C-N bond has partial double bond characteristics.
This makes it very inflexible, so we see relatively little rotation around bond, so it’s very rigid)
3) Always adopt a trans confirmation - the carbonyl oxygen and amide hydrogen are always on opposite sides of the peptide bond and the R group from adjacent amino acid residues are also on opposite sides (very important because if they were on the same side, the R groups would clash and interact and the carbonyl O and amide H would too.
4) Also, bonds either side of the peptide bond can rotate, Psi (Ca-C) or Phi bonds (Ca-N) = what determines the 3D structure of protein molecules
Describe the key features and properties of secondary structure, including why the properties of a peptide bond contribute to this
What is the secondary structure?
The local spacial arrangement of polypeptide backbone consisting of alpha helixes and beta pleated sheets
Describe the key features and properties of secondary structure, including why the properties of a peptide bond contribute to this
- Alpha helix - hydrogen bonds between N-H and C=O stabilise the structure
- Beta sheet - structure stabilised by hydrogen bonds between strands. Beta sheets can be antiparallel, parallel or mixed arrangements sheet
The Phi & Psi bond rotation allows the protein to have these 2 secondary structures and also stabilises the structure
Explain what is meant by tertiary structure
Secondary structure gets folded to form tertiary structures
Tertiary structure:
- The overall 3D structure of the polypeptide chain in space, that can involve amino acid residues from anywhere on the protein
- Either globular proteins or fibrous proteins
Explain what is meant by tertiary structure
What is the tertiary structure of globular proteins in aqueous solutions like?
- The tertiary structure of globular proteins in aqueous solution is compact, with a high density (close packing) of the atoms in the core of the molecule. Hydrophobic side chains are buried in the interior, whereas hydrophilic groups are generally found on the surface of the molecule.
Explain what is meant by tertiary structure
What does the term “Tertiary” actually refer to?
- “Tertiary” refers both to the folding of domains (the basic units of structure and function; see A. below) and to the final arrangement of domains in the polypeptide.
Explain what is meant by quaternary structure
- Association between different polypeptides to form a multi-subunit protein
- Subunits either may function independently of each other or may work cooperatively
Identify the types of bonds involved in maintaining the different levels of protein structure and (appreciate what the consequences are of their disruption)
- Primary structure - only peptide bonds (type of covalent bonding) between carboxyl group of one amino acid and the amine group of another
- Secondary structure - hydrogen bonds – bewteeen the polypeptide backbone – amide hydrogen and carbonyl oxygen
- Tertiary structure -
hydrogen bonds, ionic bonds , van der Waals interactions (the nonspecific attraction between closely packed atoms), hydrophobic interactions, and disulfide bonds. - Quaternary structure - subunits are held together primarily by non-covalent interactions for example, hydrogen bonds, ionic bonds, and hydrophobic interactions
Identify consequences of disruptions in bonds involved in maintaining the different levels of protein structure
When bonds are disrupted (denaturation) this alters the shape of the protein and thus alters the function of it, so it is unable to function properly or at all.
Recognise & draw the structure of an amino acid
Assign properties of amino acid residues based on structure
How are amino acids classified?
- They are classified according to the physical and chemical properties of their R groups
Assign properties of amino acid residues based on structure
State the chemical properties that we use to classify amino acids and state what each one means.
Hydrophobic - water hating
Hydrophilic - water loving
Polar - electrons are not equally shared, one part of the molucule is more negative than the other part
Non-polar - electrons are equally shared, not one part of the molecule is distinctively negative or positive
Acidic - COO- and COOH (negatively charged)
Basic - NH2 and NH3+
Assign properties of amino acid residues based on structure
State the physical properties that we use to classify amino acids and state what each one means.
Aliphatic - only carbons and hydrogens
Aromatic - contains a phenyl ring-like structure
In solution, at physiological pH, how do amino acids exist as?
- In solution, at physiologic pH, the free amino acids exist as zwitterions, ions in which the amino group is positively charged, and the carboxylate group is negatively charged.
Outline how proteins fold
The folding process is ordered, driven by the need to find the most stable confirmation. When it finds a conformation that works, it holds this confirmation as it makes it more stable, this then reduces the number of next available conformations
Why is folding important for protein function?
Protein folding is very important because it determines the properties of the protein and its ability to carry out a specific function
Why can protein misfiling cause disease?
Misfolding can because disease as it changes the properties/function of a protein/enzyme etc.
EXAMPLE: amyloid fibres are misfolded and become insoluble (normally soluble) and can then go on to form plaques in Alzheimers disease
Explain why some amino acid residues are charged
- If we put an amino acid into water, we get ionisation
- Our amino acid can exist in 3 different forms:
1) Protonated form (protonation of amino group AND carboxyl group/both groups gain a H+). If both groups are protonated, then only the NH3+ group has a positive charge (COOH is neural)
2) Deprotonated form (both groups lose a H+) If both groups are deprotonated, then the COO- group has a negative charge (NH2 is neutral)
3) At physiological pH, the amino acids exist in Zwitterionic form - where both the amino group and the carboxyl group are ionised, and both are charged (COO- & NH3+) - The amino group has gained a proton and is positively charged and the carboxyl group has lost a proton and is negatively charged
Describe the general structure of amino acids
- Central alpha* carbon atom covalently bonded to:
- Hydrogen atom
- Carboxyl group (COOH)
- Amino group (NH2)
- A distinctive R group (side chain)
- The carbon atom next to the carboxylate group
Explain the different properties of amino acids
Hydrophobic - water hating
Hydrophilic - water loving
Polar - electrons are not equally shared, one part of the molucule is more negative than the other part
Non-polar - electrons are equally shared, not one part of the molecule is distinctively negative or positive
Acidic - COO- and COOH (negatively charged)
Basic - NH2 and NH3+
Aliphatic - doesn’t contain a phenyl ring
Aromatic - contains a phenyl ring-like structure
Describe the key features of peptide bonds and explain how they contribute to protein structure
Explain how peptide bonds contribute to protein structure
Peptide bonds are present in the primary structure of a protein and they join individual amino acids together in order to form a polypeptide chain
An outline of how proteins fold
- All info needed for folding is contained in primary sequence
- The folding of proteins depends on the chemical and physical properties of the amino acids
- The folding process must be ordered
- Each step involves localised folding and with stable conformations maintained (once the protein adopts a localised stable confirmation, that is held - e.g. if it gets an alpha helical structure formed in the right place, that is maintained because it is more stable)
- So we lower the number of possible confirmations
- The partially folded intermediates (the molten-globule state) allows us to quickly form a fully folded protein
- Essentially driven by the need to find the most stable confirmation/the formation of stable intermediates
- It is an entropy-driven process
