Module 3: V1 - V2 Flashcards
What is the structure of myoglobin?
myoglobin is a monomer with tertiary structure
What is the structure of hemoglobin?
hemoglobin is composed of four subunits
a tetramer with quaternary structure
Which subunits is hemoglobin composed of?
hemoglobin is a tetramer of two subunits ɑ2β2
each subunit is similar to myoglobin
Which group is common to both myoglobin and hemoglobin and what is the function of this group? How is it able to do this?
the heme group which binds oxygen
contains an Fe(II) centre which coordinates the oxygen that binds
How can hemoglobin be described?
as a tetramer of four subunits or, more correctly, a dimer of two ɑβ ‘protomers’
What is a ‘protomer’?
a ‘protomer’ is the structural ‘unit’ of a protein with quaternary structure
How many subunits is IgG composed of, what are these subunits called and what is their function?
four subunits: 2 heavy chains and 2 light chains which are both involved in binding to the antigen ligand
What happens to the variable regions once they bind an antigen?
they undergo conformational (shape) change
How can IgG be described?
not so much a tetramer, more so a dimer of light chain / heavy chain pairs
What is the Fab region and how many domains is it composed of?
the fragment that allows for antigen binding
it is composed of four domains
What is the immunoglobulin-like fold composed of?
a sandwich of two beta-sheets
Where is the variable domain found?
one at each of the two tips of the antigen binding region
Why have antibodies evolved to be multivalent?
multivalent binding is more effective due to ‘avidity’
Why has hemoglobin evolved to be multimeric (bind more than one oxygen)?
not just simply that it can bind four times more oxygen as myoglobin
cooperative binding occurs in hemoglobin resulting in a sigmoidal graph of saturation with O2 against pO2
this can only happen in a multimeric complex
What are the two functions of myoglobin?
storage of oxygen in muscles and release of oxygen when rapidly contracting muscle needs energy
Where does oxygen bind to in the myoglobin protein?
the heme group
Why are diving animals e.g. seals, otters and whales able to breathe for long periods underwater?
when starting to dive, they slow their heart rate, stop breathing, and shunt blood to the brain, heart, and muscles
the myoglobin concentration in muscles of diving mammals is ~10x that in humans
Why is myoglobin positively charge in elephant seals?
so the molecules repel each other and do not clump at high concentration
What is a common function of many proteins?
many involve the binding of another molecule - in the case of myoglobin, that molecule is oxygen
What is oxygen referred to in terms of binding and where does it bind to on the protein?
oxygen is called a ligand and the ligand attaches to the binding site of the protein
How does O2 bind to myoglobin?
binds reversibly to Fe2+ of the heme prosthetic group
What type of coordination complex does oxygen form with the heme prosthetic group?
octahedral
What is the equilibrium association and dissociation constant for an arbitrary system of A + B ⇌ AB?
Ka = [AB]/[A][B], units M^-1 Kd = [A][B]/AB, units M
Is the dissociation or association constant preferred in biological sciences? Why?
the dissociation constant because it is useful in expressing ligand binding as it represents the concentration of a ligand at which the protein is 50% saturated (Kd)
What is given by theta? Give the equation.
occupied protein sites divided by total protein binding sites
θ = [PL]/[P] + [PL]
θ = [L]/[L] + Kd
What is biotin?
a vitamin which must be provided in the diet and is needed for decarboxylations
binds the protein avidin found in raw egg white of which the Kd is 10^-15 (almost irreversible)
What is biotin deficiency associated with in humans?
long-term consumption of diets rich in raw eggs
the biotin-avidin complex survives digestion and is lost in faeces
You read a research article that that says the epidermal growth factor (EFG) receptor binds its ligand with a Kd of 1 nanomolar. Generally speaking, is that weak intermediate or strong binding?
strong binding
A truncated mutant version of the receptor (missing some of its sequence) binds EGF with a Kd of 0.2 micromolar. Does the mutant bind EGF more strongly or more weakly than the wild type receptor?
more weakly
A diet overly rich in raw eggs can lead to biotin deficiency. Cooked eggs do not cause this problem. Why?
avidin is denatured during the cooking process which means that it can no longer bind to biotin in the body, therefore this will not be an issue
