Lecture 2.5: Structure & Function of Transporters

Question 1

K+ channels consit of [–] that fit together to form a [–] channel

Answer 1

alpha-helices, selectivity channel

Question 2

What is responsible for the selecitivity of the K+ channel?

Answer 2

the placement of the carbonyl oxygens within the selectivity channel (responsible for ion selectivity)

Question 3

Why is glycine important for selectivity in the K+ channels?

Answer 3

• hydrogen function group allows unique helical structure to form
• they have dihedral angles that allow for carbonyl oxygen atoms in the protein backbone to point towards the ions

Question 4

what is the selectivity ratio of K+ to Na+

Answer 4

1000 to 1

Question 5

Na+ and K+ differ only slightly in [–]

Answer 5

atomic radius

Question 6

What is the hydration #, interaction, and hydrated ionic form

Na+

Answer 6

• 5-6
• strong
• 6.62 Å

Question 7

What is the hydration #, interaction, and hydrated ionic for

K+

Answer 7

• 7-9
• weak
• 7.16 Å

Question 8

Why is K+ selected over Na+?

Answer 8

once unhydrated, the Na+ does not form equivalent interactions with the carbonyle oxygen

Question 9

Charbdotoxin and Dendrotoxin block K+ channel function by?

Answer 9

• making the ends positively charged and repelling positive K+ from entering
• makes it so that the channel can only interact with negatively charged amino acids

Question 10

Mammalian aquaporin proteins

Answer 10

• regulate H2O transport in the kidneys
• fluid transport in the lens of the eye
• control H2O homeostasis in the brain

Question 11

[–] transmembrane [–] form water channels through the membrane

Answer 11

6, alpha helices

Question 12

What amino acid is essential for selecitivity in aquaporins?

Answer 12

Asn (asparagine)

Question 13

[–] makes up the constriction point in aquaporins

Answer 13

Asn residues

Question 14

What are the common features of auqaporins?

Answer 14

• multi-domain proteins
• possess a selectivity filter
• specialized strucutures for passive transport
• not saturable

Question 15

Primary active transporters

Answer 15

use energy directly derived from ATP hydrolysis

Question 16

secondary active transport

Answer 16

use energy available from a downhill electrochemical gradient generated by primary active transporters

Question 17

antiporters

Answer 17

move two molecules across a membrane in different directions

Question 18

symporters

Answer 18

move two molecules across a membrane in the same direction

Question 19

What is SERCA responsible for?

Answer 19

transporting Ca2+ ions from the cytoplasm into the SR lumen to promote muscle relaxtion

Question 20

What is SERCA responsible for?

Answer 20

transporting Ca2+ ions from the cytoplasm into the SR lumen to promote muscle relaxtion

Question 21

What is Ser16 phosphorylated by?

Answer 21

protein kinase A

Question 22

what phosphorylates Thr17

Answer 22

Ca2+/calmodulin kinase II

Question 23

what stimilates the phosphorylation of Ser16

Answer 23

epinephrine

Question 24

what stimulates the phosporylation of Thr17

Answer 24

high levels of cytosolic Ca2+

Question 25

The Ca2+ transporting activity is controlled by [–] of phospholamban

Answer 25

phosphorylation

Question 26

Steps of SERCA

Answer 26

1. inactive complex = unphosphorylated phospholamban
2. phosphorylation of phospholamban
3. dissociation of complex
4. channel opens on SERCA protein, allowing Ca2+ to enter SERCA
5. SERCA is desphosphorylated and ADP is released
6. Ca2+ released
7. muscle relaxation
8. ADP is phosphorylated
9. inactive complex

Question 27

4 Step Ca2+ transport model

Answer 27

1. Asp351 phosphorylation = Ca2+ binds to Asp351 residue in M2 domain –> hydrogen ions released –> N domain conformational change = reduced ATP affinity
2. ADP dissociates, causing M2 to release Ca2+ and the N domain goes through a conformation change to restore affinity for ATP
3. ATP binds to N domain again which causes the M2 domain to reposition and trap H+
4. Asp351 dephosphorylates

Question 28

NaK Pump moves [–] Na+ [–] and [–] K+ [–]

Answer 28

3 Na+ out of cell
2 K+ in cell
ATP to ADP

Mnemonic: “3-2-1-N-O-K-I-A”