Jeuken Flashcards
How is water transported into a cell?
down 55M gradient by free diffusion or facilitated diffusion through aquaporins
for simple diffusion: -Gibbs can be what kind of movement regarding electrochemical or concentration gradient?
down concentration gradient or up concentration gradient if down electrochemical gradient
what substances can move by free diffusion?
lipophiles and gases dissolved in solvents
what is partition?
hydrophobicity
aminos-sugars-aliphatics have _ _creasing permeability and hydrophobicity
increasing
what are the 4 types of protein transporters?
Ion channels, ATP powered pumps, transporters, pores
How many strands make up a beta-barrel
8-22 strands, mostly homotrimers of 16-18 strands
beta-barrels are used for what tpe of transport
pores for simple diffusion
ompX is a beta barrel for what function?
membrane bound adhesion receptor
lipocalin retinoid receptor is what type of protein?
soluble beta-barrel
which residues are exposed at beta-barrel faces?
~40% aromatics interact with phospholipids
where are TM beta barrel pores found?
mitochondria, chloroplast, gram negative bacteria
what do Omp proteins do?
pores in E.coli with weak cation selectivity provided by acidic residues in the filter.
what are the examples of b-barrel pores?
PhoE, Omp, Lamb, FepA&FhuA
What are the 2 types of simple diffusion proteins?
Gap junctions, beta barrels
what is the structure of a gap junction?
6 subunits x 4TM alpha helices. Phosphorylation regulates opening, connexin mixtures regulate pore size
What are the 4 classes of ATP powered pumps?
P, V, F ATPases; ABC
what energy drives active transport?
Voltage gradient or ATP
what is the structure of P class ATPases?
2 independent, identical alpha subunits containing pump, Aspartate for phosphorylation and ATP binding domain.
What is the mechanism of active transport proteins?
Alternating access driven by ATP hydrolysis and phosphorylation altering conformation and substrate affinity.
What is the structure of ABC transporters?
1-4 peptides with 2 cytoplasmic NDB, 2 TM domains totalling 6 helices up, 6 helices down.
What are examples of ABC transporters?
Mdr1 (multi drug),
MalK (maltose),
CFTR,
BtuC (Vitamin B12)
Which proteins mediate facilitated transport?
ion channels, uniports, symports, antiports.
What is the structure of passive transporters?
12 TM inverted repeat with substrate binding pocket
what is the mechanism of passive transporters?
occlusion alternate access
what are examples of passive transporters?
Glut1 (glucose uniport),
XylE (D xylose, H+ symport),
Mph1 (hydantion Na+/H+ symport)
BetP (betaine with choline antiport or Na+ symport)
where are GLUT1 transporters?
RBC and BBB.
what disease is associated with GLUT1 mutations?
de vivo neurological disorder
Where are GLUT4 transporters?
uniporters into muscle cells expressed on insulin stimulation
Where is SGLT1?
Na+ symport from gut, gradient maintained by Na/K pumo
Where is SGLT2?
reabsorption from kidney
what are the 5 families of multidrug resistance efflux pumps?
ABC uniports MATE Na+ antiport MFS H+ antiport SMR H+ antiport RND
where are drug efflux pumps found?
bacterial membrane, coupled to TolC in Gram negative
What type of transport do ion channels mediate?
specific but passive
Where are ion channels found?
All kingdoms
what is the structure of ion channels?
4 subunits x 6TM helices + P loop for selectivity filter
What does KcsA transport?
K+ in hydrated state
what is the structure of KcsA?
4 subunits x 2TM helices with P loop coordinating TVGYG selectivity filter which binds 2K using oxygen to coordinate
how many K does KcsA transport?
3: 2 in selectivity filter and a hydrated one in channel
What is the structure of the Kv1.2 channel?
4 subunits x 6TM helices and P loop.
250 residue N terminal, 150 residue C terminal domain
4Arg sensor in helix 4
Glycine hinge in helix 6 opens channel
how is the Kv1.2 channel spontaneously inactivated?
intrinsically disordered N terminal ball has 10 residues to enter channel and 10 residues for hydrophilic T1 domain
Where is Kv1.2 found?
eukaryotes for action potential
What signalling is NavAB channel used in?
nociception
what 3 forms does NavAB exist in?
closed, pre-open (helix 5 gating hinge open), open (glycine hinge open)
What are TRP channels?
weakly selective cation transporters involved in senses
what structure do TRP channels have?
tetramers of 6 TM helices but low homology to v-gated channels.
what are the 7 TRP families?
C,V,M,A,ML,P,N
which TRP channel is involved in taste?
M5
What does M5 TRP channel detect?
Calcium released from ER by GPCR opens channel for depolarisation by Na influx.
Also detects voltage and temperature.
which neurons do TRP receptors integrate into?
Trigemal and dorsal root ganglions
Which TRP channel detects hot substances?
V1
Which TRP channel detects cool substances?
M8
Which TRP channel detects pungent substances?
A1
Which TRP channel is selective for Ca?
A1
Which TRP channel detects inflammation?
A1, V1
Why is CTFR unusual?
homology based ABC structure of 2NBD and 2TM inverted repeat BUT ION CHANNEL
How does ATP act on CFTR?
R domain phosphorylation increases affinity for Cl- substrate by bringing NBDs together.
