Mitochondrial Transporters Flashcards
Where does ATP production occur?
In the matrix of mitochondria
Where are metabolite transporters found in the mitochondria?
In the inner-membrane
What is the general structure of mitochindrial metabolite transporters?
A conserved protein fold of 6 transmembrane helices
What drives the mitochondrial ATP/ADP carrier?
Membrane potential
What kind of transporter is the mitochondrial ATP/ADP carrier?
Antiporter
What does an electrogenic transporter mean?
A transporter results in a net movement of charge across the membrane
What is the direction of transport of ATP in the mitochondrial ATP/ADP carrier?
ATP out of the mitochondria
What is the direction of transport of ADP in the mitochondrial ATP/ADP carrier?
Into the mitochondria
What is the change in charge every time the mitochondrial ADP/ATP carrier moves?
lose -1 charge
How many ATP are transported into the mitochondria for 2 ADPs by the mitochondrial ADP/ATP carrier?
3 ATPs
What is the structure of the mitochondrial ADP/ATP carrier?
- 6 transmembrane helices arranged in 3 x 2 helix repeats
What do amino acids do the 2 helix repeats found in the mitochondrial ADP/ATP carrier often contain?
Proline and glycine
Why do the 2 helix motifs of the mitochondrial ADP/ATP carrier often contain glycine or proline?
Proline and glycine induce kinks/flexibility which allows the helices to be very dynamic
Why is it important for transport helices to be very dynamic?
So they can re-orient and undergo conformational changes
Why does proline introduce kinks and flexibility into protein helices?
- Lacks an avaliable NH group to form helical hydrogen bonds
- Contains a bulky 5 member ring
How does the alternate access model work for the mitochondrial ADP/ATP carrier?
- ADP binds, transition occurs and re-opens to face the matrix side
- ADP diffuses into the matrix
- ATP can then bind, transition occurs and re-opens to face the cytoplasm side
- ATP diffuses out
What was used to provide a matrix open state of the mitochondrial ADP/ATP carrier?
- BKA
- Protein from thermphilic organisms
- Nanobody
How did BKA help to give a martrix open structure of the mitochondrial ADP/ATP carrier?
It inhibited the carrier
How did using the mitochondrial ADP/ATP carrier from a thermophilic organism help to get a matrix open state?
- Proteins from thermophilic organisms tend to be mostly functional at high temperatures
- When cooled they tend to be more solid and ordered so easier to get a nice crystal
How does the channel in the mitochondrial ADP/ATP carrier reorganize itself in transitions between open states?
- Binding sites stay in a constant with respect to the membrane
- Pivots to reorient access between matrix and cytoplasm
How does the mitochondrial ADP/ATP carrier attract ATP on the matrix side?
There is a really positive surface exposed
What drives the mitochondrial phosphate/H+ symporter?
pH gradient
Is the mitochondrial phosphate/H+ symporter electroneutral? Why?
yes because H+ and phosphate (-1) are transported together
Does the mitochondrial ADP/ATP carrier use PMF?
No
Does the mitochondrial ADP/ATP carrier use membrane potential?
Yes as it moves 1 charge but no H+
Does the mitochondrial phosphate/H+ symporter use some of the H+ gradient?
Yes as it moves 1H+
How many H+ does ATP synthase use per ATP?
3-5
Per ATP generated how much charge and how many H+ are used for ADP/ATP/Pi overall transport?
1H+ and one charge