Protein Structure Flashcards
(42 cards)
Properties of peptide bonds
Very stable
Cleaved/broken by PROTEOLYTIC enzymes- proteases or peptidases
Partial double bond (slide 4)
Flexibility around C atoms not involved in bond, allows multiple conformations/shapes
Usually one preferred native conformation, determines mainly by the type of side chains and their sequence in the polypeptide
Protein is…
Large polypeptide, usually from a few 10s to 1000s amino acids
Large variety of functions because of the large number of different 3D shapes
Function of protein is completely dependant on structure
Representing polypeptides as a Backbone
A line following the peptide bonds
Cartoon
A representation showing the fundamental secondary structures (helix/sheet)
Forces that hold proteins together
Van der Walls forces
Hydrogen bonds
Hydrophobic forces
Ionic bonds
Disulphide bonds
Van der Waals forces
Weak attractive interactions between atoms due to fluctuating electrical charges.
Only important when two macromolecular surfaces fit closely in shape.
Can also be repulsive at very short distance
Hydrogen Bonds
Interaction between dipoles, involving an hydrogen and an oxygen/nitrogen
Partial negative charges on negative atoms e.g. O and N bound to H, which then has a partial positive charge.
These partial charges allow weak attractive interactions between some amino acid side chains, main-chain O and N and water.
Hydrophobic forces
Uncharged and non-polar side chains are poorly soluble in water and are effectively “repelled” by water.
These hydrophobic side chains tend to form tightly packed cores in the interior of proteins, excluding water molecules.
This attraction is the “hydrophobic force”
Ionic Bonds
Occur between fully or partially charged groups.
Weakened in aqueous systems by shielding by water
molecules and other ions in solution.
Disulphide bonds
very strong covalent bonds between sulphur atoms
In extracellular domains of proteins.
Conditions can be harsher so extra stability is conferred by covalent bonding between side chains of cysteine residues
Cysteine (slide 11)
Primary structure
Linear sequence of aa linked by peptide bonds (covalent bonds)
• While in itself does not tell very much about fuction, fuctionally and evolutionarily related proteins may have similarity - and identify motifs
• The primary structure of a protein determines its 3D conformation, i.e. dictates the way in which the chain will fold to form its native structure.
Chaperones
Proteins that assist other proteins in reaching their conformation after translation themselves
Secondary structure The a - Helix
H-bonds between each carbonyl group and the H attached to the N which is 4 aa along the chain
Side chains look outwards
Proline breaks the helix (ring + no H)
Secondary structure. The b - sheet
• Formed by H-bonds between linear regions of polypeptide chains.
• Chains from two proteins, or same protein. Parallel or antiparallel chains, pleated or not .
If the chain is folding back, structure is usually a 4 aa turn, called hairpin loop or b-turn.
Tertiary Structure
This is the overall 3D conformation of the protein.
Forces involved include electrostatic, hydrophobicity, H-bonds, and covalent bonds.
Some conformational domains occur repeatedly, and include barrels, bundles and saddle.
Folding of the secondary structure into a globular structure due to bonds such as ionic bonds, disulphide bridges and Van der Waal forces.
Conformations can change with pH, T etc.
Quaternary structure
Three dimensional structure of a protein composed of multiple subunits.
Same non- covalent interactions as tertiary structures.
2 or more tertiary structures joined together to form a protein e.g. haemoglobin
Enzymes (slides 22-28)
Proteins that work as catalysts, enable reactions to occurs that otherwise would not be able to occur at physiological (body) temperatures and conditions
Enzymes bind the reactants (substrates) and convert them to products. Then they release the products and return to their original form
Not only they speed-up the reactions, but provide a way to regulate the rate of reactions
Enzymes provide an alternative reaction pathway with a lower activation energy
Can be used as: disease markers, drug targets
Porphyrin Ring (slide 32-35)
• At the core of the molecule is porphyrin ring which holds an iron atom.
• An iron containing porphyrin is termed a heme.
• This iron atom is the site of oxygen binding.
• The name hemoglobin is the concatenation of heme and globin
Factors Influencing Hemoglobin Saturation
Temperature, H+, PCO2 :
All Modify the structure of hemoglobin and alter its
affinity for oxygen
– Increase:
• Decrease hemoglobin’s affinity for oxygen • Enhance oxygen unloading from the blood
– Decrease act in the opposite manner.
All these parameters are high in peripheral capillaries where Oxygen unloading is the target.
Sickle Cell anemia
Sickle Cell Anemia is a genetic disorder that is characterized by the formation of hard, sticky, sickle-shaped red blood cells, in contrast to the biconcave-shaped red blood cells (RBCs) found in “normal” individuals.
Cause of sickle cell anemia
This disease is caused by a mutation in hemoglobin.
Immunoglobulins (Antibodies)
Antibodies are produced to bind antigens, typically toxins or proteins on the surface of microbial agents.
These targets are consequently labelled for destruction by cells of the immune system or by lysis or through the complement system
Diagram on slide 45
Immunoglobulin Structure (slide 46-47)
The immunoglobulin fold structure of antibodies comprises a supporting scaffold (framework regions) that serves to display highly variable loops of complementarity determining regions – (CDRs)
The diverse nature of CDR regions enables a range of reversible bonding effects (hydrogen bonds, Van der Waal forces) to act between antibody and antigen
Antigen Recognition
The essence of antibody/antigen interaction is the very close proximity of the antibody CDR regions and the antigen surface
Intimate contact allows the combination of relatively weak interactions to produce a strong binding surface
The CDR loops have a sequence of amino acids that “complement” the surface of the antigen
