2:Protein structure and function Flashcards
List some examples of proteins
Insulin - Regulates blood glucose levels
Interleukin-2 (IL-2) - Regulated aspects of immunity
EPO - Stimulates the production of red blood cells
TNF-alpha - Mediator of inflammation and immunity
Haemoglobin - Gas transport
What are the different types of proteins? Give examples of each.
Structural proteins Eg; Cytoskeleton and bone
Enzymes Eg; Catalyse chemical reactions
Plasma membrane proteins Eg; Pumps, channels, receptors.
Others; Eg; Antibodies, toxins, hormones, fibres etc.
What are the 3 special amino acids?
Cysteine - Sulphydryl group side chain, allows it to oxidise and form a disulphide bond with another cysteine residue.
Glycine - Small size allows it to fit into tight spaces
Proline - Contains a cyclic ring which makes the amino acid more rigid, creating a fixed kink in a protein chain.
Describe the polarity arrangement on the polypeptide chain backbone.
The polypeptide backbone consists of amino acids with polar and non-polar side chains that alternate along the length of the back bone. Polar aa’s - Lysine, Arginine
Non-polar aa’s - Glycine, Leucine
Non-charged aa’s - Serine, Asparagine
What is meant by the backbone steric limitation?
Each amino acid contributes 3 bonds to the backbone chain, but the peptide bonds do not allow for rotation. Therefore, rotation can only occur around the Ca-C and N-Ca bones. This only allows a few angle combinations hence there are less possible conformations
Identify and describe the forcing influencing peptide folding.
Non-covalent interaction;
Van der waals attractions - weak bonding interactions due to their fluctuating electric charges
Hydrogen bonding - Electropositive H atom partially shared by two electronegative atoms
Ionic interactions - Electrostatic attraction between oppositely charged ions.
Hydrophobic force - Dependent on the distribution of polar and non-polar amino acids. The hydrophobic core region contains non-polar side chains, while the polar side chains on the outside of the molecule, allowing for hydrogen bonds to form with water molecules.
Covalent Interactions;
Covalent cross-linking - Can only occur in oxidative environments. It involves di-sulphide bonds attaching to 2 polypeptide chains, stabilising the internal folded structure.
Explain the protein folding pathways.
Newly synthesised proteins attain a ‘molten globule’ state when the secondary structure is not well packed. This protein is pushed to the off-pathway folding process where proteins called chaperones unwrap and correct the ‘mis-folded’ protein. If it can’t be corrected, the protein is degraded by proteases into its amino acid components.
What is the role of a chaperone?
Chaperones add reliability to the spontaneous folding of a protein. They are required to ensure the correction of mis-folded proteins and preventing hydrophobic regions of proteins aggregating with each other.
Mis-folded proteins occur due to the small size of the cytoplasm and the large number of proteins that are being synthesised at any one time.
Describe the 3 local folding areas. Alpha-helices, Beta-sheets and loops/turns.
Alpha-helices - links the C-O and N-H of amino acids via a H-bond. The peptide backbone twists to form a helix with 3.6 amino acids per turn. The side chains point outwards and determine the hydrophobic/hydrophilic nature.
Beta-sheets - Formed by H-bonding between backbone atoms in adjacent strands. These can be orientated parallel or antiparallel. Side chains can be projected from both sides of the sheet.
Loops/Turns - Connect the helices and sheets. They loops are unstructured areas, but turns are the highly structured areas; Consisting of 4-5 amino acids looped into a U-shape stabilised by the internal H-bonds.
What are motifs?
Motifs are a group of elements in a regular secondary structure. The same motifs often appear in different proteins that conduct similar functions. These super-secondary structures are a combination of helices and sheets that include DNA binding and are often located in transcription factors.
What are the two different structures of tertiary proteins?
Globular - Intracellular soluble proteins. Not very organised
Fibrous - Extracellular proteins and the cytoskeleton. Organised.
What is the domain of a tertiary protein?
The domain is a polypeptide chain that can independently fold into a stable and compact tertiary structure. It usually consists of 40-350 amino acids that can be used to construct larger proteins associated to a specific function.
What is the quaternary structure of a protein?
The quaternary structure consists of 2 or more tertiary polypeptide chains that combine to form a functional proteins. Eg Haemoglobin.
What is the proteosome and what is it’s role?
The proteosome degrades misfolded proteins that are unable to be repaired by chaperones. The mis-folded protein is targetted by polyubiquitin chains. These chains are released once the protein has entered the proteosome. As the protein passes through the proteosome active site, it is degraded and released out the proteosome cap as component amino acids.
