Major Facilitator Superfamily Flashcards
What kind of transport does the major facilitator superfamily do?
Passive or secondary active transport
What functions does the major facilitator superfamily complete?
- Nutient Uptake
- Signal transduction
- Drug and noxious compound extraction
Name a member of the major facilitator superfamily
Lactose Permease
Where is lactose permease found?
In the cytoplasmic membrane of bacteria
What is the function of lactose permease?
It transports lactose into the cell when the concentration of glucose is low
What forms the substrate binding pocket of lactose permease?
Network of hydrogen bonds from charged residues
Which amino acid is particularly important in binding sugars?
Tryptophan
Why is tryptophan particularly important in binding sugars in lactose permease?
Because the sugar ring is able to stack on the tryptophan sidechain
How is lactose permease powered?
By translocating H+ from the periplasm to the cytoplasm down a concentration gradient, producing an electrochemical gradient
Where is the lactose transported from and to?
From periplasm to the cytoplasm
Why are His, Asp, and Glu likely to be involved in the proton pathway of lactose permease?
- Can be reversibly protonated
- pKa around physiological pH
What does the lac permease face in the outward conformation?
Periplasm
Where does the lac permease face in the inward conformation?
Cytoplasm
Does H+ or lactose bind first
H+
What happens once H+ and lactose have both bound to the lac permease?
The transporter undergoes a conformational changes where it flips from an out to inward conformation
In the outward conformation of lac permease there is a hydrogen bond between which amino acids?
R144 and E126
In the outward conformation of lac permease H+ is bound to which amino acid residue?
E269
In the inward conformation of lac permease H+ is bound to which amino acid residue?
In the inward conformation of lac permease there is a hydrogen bond formed between which two amino acids?
R144 and E269
What is the effect of changing conformation from outwards to inwards in lac permease on affinity for lactose?
Causes the lactose binding site to go from a hugh affinity to a low affinity
What is the purpose of the conformational change decreasing the affinity of the lactose binding site in lac permease?
It allows the lactose to be released
Once lactose has been released what happens to lac permease?
H+ comes off and the inward facing unbound transporter flips back to become outward facing
What does the confomational change from outward to inward of lac permease require?
Both H+ and Lactose to be bound
What regulates H+ affinity in lac permease?
Changes in the pKa’s of residues
What modulates ligand affinity in lac permease?
Changes in binding site conformation
What is the main function of GLUT 1 transporters?
Uptake of glucose from blood to cells
What kind of transporter is GLUT1?
A passive uniporter
What is GLUT1 composed of?
Bundles of transmembrane alpha helices
What transporter has a very similar structure to GLUT1?
bacterial xylose:H+ symporter
What is mapping of mutations in transporters useful for?
Designing drugs
