Lecture 2.2: Soluble Transport Proteins Flashcards
Myoglobin is a good oxygen [–] protein
storage
Sigmoidal O2 binding patterns
sigmoidal curve = oxygen is a good TRANSPORTER
higher pO2 = loading of O2
lower pO2 = release of O2
When O2 is unbound what is the conformation of heme?
DeoxyHb = puckered heme
when O2 is bound what is the conformation of heme?
OxyHb = planar heme
When O2 is bound what happens to the conformation of His F8 and F helix
the His F8 and F helix move towards the heme, resulting in tertiary structure
T-state trends
tense = deoxyhemoglobin = unbound form = low affinity for O2
R-state trends
relaxed = oxyhemoglobin = bound form = high affinity for O2
A hydrogen bond between [–] and [–] stabilizes the T-state?
Asp99 carboxylic group and Tyr42 hydroxyl group
A hydrogen bond between [–] and [–] results in R-state stabilization?
Asp94 carboxylic group and Asn102 amino group
Concerted Model
Little to no ligand is bound
T-state favored
Concerted Model
ligand binding shifts the entirew tetramer simultaneously from [–] to [–]
T to R
Concerted Model
Binding of ligand [increases or decreases] the population of [–] state
increases, R
Concerted or Sequential Model
The last O2 binds with [–]x [–] affinity than the first
100x higher
FULLY OXYGENATED
Sequential Model
Ligand binding to one subunit induces conformation change of [–] subunit to the [–] state
adjacent, R
Sequential Model
Two states can exist in the [–] tetramer
same
Steps for O2 cooperativity
- O2 binds to first tetramer
- Fe2+ moves into heme
- F-helix (his) shifts
- bonds rearrange at interfaces
- fully saturated
how can affinity for O2 change?
- Protein has multiple ligand sites
- binding of effector molecules induces conformational change
- conformational changes are translated to neighboring ligand binding sites, influencing their affinity for ligand
- protein shifts between two conformations: high and low affinity
cooperativity is recognized by what type of curve?
sigmoidal
if the hill coefficent is >1 what us the cooperativity?
positive
if the hill cofficient is <1 what is the cooperativity?
negative
if the hill coefficent is =1 what is the cooperativity?
none
positive cooperativity
the first binding increases the affinity of the second site
(hemoglobin)
negative cooperativity
the first binding event decreases the affinity for the second site
no cooperativity
myoglobin
Heterotropic/ Allostery
Effector binds to secondary sites & influences binding of the ligand at the primary site
Homotropic/Cooperativity
ligand binds to one site & influences binding of the same ligand at a different site
What happens to the o2 saturation curve when in high temps?
shifts right = decreased affinity
what happens to the O2 saturation curve when in low temps
shifts left = increased affinity
Three ways to remove CO2
- dissolved CO2 gas
- dissolved bicarbonate (80-85%)
- bound to hemoglobin
Low pH favors [–] state and [–] O2 affinity
T, decreases
H+ is a [–] effector
heterotropic allosteric
increased H+ = [–] pH = [–] binding affinity
decreased pH, low binding affinity
How does bicarbonate stabilize T-state
binds to the N-termini of Hb subunits
carbamylating further [–] and produces and additional [–] in O2 saturation of Hb
stabalizes the T-state, decrease
CO2 is a [–] effector
negative heterotropic allosteric effector
2,3 BPG interacts with?
K, R, H
lysine, arginine, histadine
2,3 BPG is negatively charged
2,3 BPG is a [–] effector
negative heterotropic allosteric effector
When 2,3 BPG levels are normal what is the difference in fractional saturation in the lungs?
33%
When 2,3 BPG levels are elevated what is the difference in fractional saturation in the lungs?
~40%
Slow Metabolic Rate Trends
decrease temp = decrease CO2 = increase pH = decrease 2,3 BPG
Fast Metabolic Rate
increased temp = increased CO2 = decreased pH = increased 2,3 BPG
