Lecture 2.5: Structure & Function of Transporters Flashcards
K+ channels consit of [–] that fit together to form a [–] channel
alpha-helices, selectivity channel
What is responsible for the selecitivity of the K+ channel?
the placement of the carbonyl oxygens within the selectivity channel (responsible for ion selectivity)
Why is glycine important for selectivity in the K+ channels?
- 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
what is the selectivity ratio of K+ to Na+
1000 to 1
Na+ and K+ differ only slightly in [–]
atomic radius
What is the hydration #, interaction, and hydrated ionic form
Na+
- 5-6
- strong
- 6.62 Å
What is the hydration #, interaction, and hydrated ionic for
K+
- 7-9
- weak
- 7.16 Å
Why is K+ selected over Na+?
once unhydrated, the Na+ does not form equivalent interactions with the carbonyle oxygen
Charbdotoxin and Dendrotoxin block K+ channel function by?
- 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
Mammalian aquaporin proteins
- regulate H2O transport in the kidneys
- fluid transport in the lens of the eye
- control H2O homeostasis in the brain
[–] transmembrane [–] form water channels through the membrane
6, alpha helices
What amino acid is essential for selecitivity in aquaporins?
Asn (asparagine)
[–] makes up the constriction point in aquaporins
Asn residues
What are the common features of auqaporins?
- multi-domain proteins
- possess a selectivity filter
- specialized strucutures for passive transport
- not saturable
Primary active transporters
use energy directly derived from ATP hydrolysis
secondary active transport
use energy available from a downhill electrochemical gradient generated by primary active transporters
antiporters
move two molecules across a membrane in different directions
symporters
move two molecules across a membrane in the same direction
What is SERCA responsible for?
transporting Ca2+ ions from the cytoplasm into the SR lumen to promote muscle relaxtion
What is SERCA responsible for?
transporting Ca2+ ions from the cytoplasm into the SR lumen to promote muscle relaxtion
What is Ser16 phosphorylated by?
protein kinase A
what phosphorylates Thr17
Ca2+/calmodulin kinase II
what stimilates the phosphorylation of Ser16
epinephrine
what stimulates the phosporylation of Thr17
high levels of cytosolic Ca2+
The Ca2+ transporting activity is controlled by [–] of phospholamban
phosphorylation
Steps of SERCA
- inactive complex = unphosphorylated phospholamban
- phosphorylation of phospholamban
- dissociation of complex
- channel opens on SERCA protein, allowing Ca2+ to enter SERCA
- SERCA is desphosphorylated and ADP is released
- Ca2+ released
- muscle relaxation
- ADP is phosphorylated
- inactive complex
4 Step Ca2+ transport model
- Asp351 phosphorylation = Ca2+ binds to Asp351 residue in M2 domain –> hydrogen ions released –> N domain conformational change = reduced ATP affinity
- ADP dissociates, causing M2 to release Ca2+ and the N domain goes through a conformation change to restore affinity for ATP
- ATP binds to N domain again which causes the M2 domain to reposition and trap H+
- Asp351 dephosphorylates
NaK Pump moves [–] Na+ [–] and [–] K+ [–]
3 Na+ out of cell
2 K+ in cell
ATP to ADP
Mnemonic: “3-2-1-N-O-K-I-A”
