Cooperativity and Allosteric Regulation Flashcards
myoglobin type of protein
monomer
hemoglobin type of protein
dimer of dimers (ab)
hemoglobin subunits are _____ to myoglobin and derived from
homologous, same evolutionary ancestor
origin of human o2 binding proteins
diversification of Mb/Hb by gene duplication
Why are multi-subunit o2 proteins common across the tree of life?
evolutionary advantage conferred by cooperative switching between high + low affinity
type of curve for myoglobin and why
hyperbolic, o2 storage
type of curve for hemoglobin and why
sigmoidal, o2 transport
cooperative phenomena involves interactions between binding sites of a given subunit and
other, equivalent binding sites in the structure
allostery
protein must transmit the signal that another ligand has bound to affect a different portion of the molecule
does mb have any allostery
no
why can hb have allosteric effects
quaternary structure
how does a polypeptide binding a ligand affect structure in hb
changes structure of another polypeptide to favor binding. communicates structural changes that allow both to bind ligand more efficiently
tense
deoxy-Hb
relaxed
oxy-Hb
changes in structure bc of o2 binding
- movement of F helix
- breaks salt bridges between subunits
- narrows cavity between subunits
when does structure shift happen
after o2 binding to only one or a few subunits to pre-organize o2 binding sites in other subunits
o2 binding pulls ____ closer
proximal His
o2 binding shifts the _______
F helix position
o2 binding _________ the heme
flattens
_____ that ____ T state structure are broken in transition to R state
salt bridges, constrain
in the sigmoidal curve, the same delta po2 gives
larger delta theta
the sigmoidal cooperative binding curve is a hybrid btwn
two hyperbolic binding curves
Monond Wyman Changeux (Concerted) model
binding of o2 to one or more subunits favors all or none transition from t to r state for all subunits, increasing o2 affinity
slope (n) =
Hill coefficient degree of cooperativity
n=1 Hill coefficient
normal binding
n>1 Hill coefficient
cooperative
n less than or equal to
number of protein subunits
on the hill plot, the curve starts to act like hyperbolic curve at
very high or low po2
anything that stabilizes T state relative to R state ____ affinity or activity of the population
decreases
allosteric regulators of Hb
o2, h+, CO2, BPG
Bohr effect equation
Hb(R) + H <-> HHb(T) w/ protonated hemoglobin
H+ binding favors the _____ (____ o2 affinity) state
tense, low
o2 and h+ are bound by Hb in an ____ manner, Hb tends to _____ protons upon binding o2
inverse, release
does h+ interact directly with heme or oxygen?
no
H+ changes the ________ of specific groups on the protein, especially
ionization, histidine
Bohr effect in tissues
at the po2 in tissues, increasing H+ decreases the fractional saturation, driving o2 off Hb
H+ binding favors _________
t state salt bridges
why does His become protonated at ph 7.4 instead of 6.0
protein microenvironment
high co2 content of respiring tissues
lowers o2 affinity
decreases pH slightly
increases h+
when o2 is released by hb
co2 is converted into carbonate
h+ is taken up by hb
co2 affect on o2 affinity
decreases hb affinity for o2
Co2 reversibly forms a _____ to _________, yielding ________
covalent bond, a-amino group at N-term of each of the 4 chains, carbamino-Hb
which structure does co2 change favor
t state
BPG is ______ at high altitude
upregulated
BPG affect on affinity
decrease hb affinity for oxygen
at higher altitude
more bpg, weaker o2 binding, more o2 released
bpg binds ______
between hb subunits
bpg charge
negative
amino acids around bpg binding site charge
positive
bpg equation
bpghb(t) + o2 <-> Hb(R)o2 + BPG
fetal erythrocytes contain
HbF
HbF has _____ o2 affinity than HbA
higher
variation in b chain that causes sickle cell anemia
glutamate to valine
new ___________ between hemoglobin tetramers leads to _______ at low po2 in sickle cell anemia
sticky hydrophobic packing, aggregation
what state is sickle cell anemia cells stuck in
t state, can’t transport o2 efficiently
