membrane proteins Flashcards
are membranes flexible
yes
are membranes self sealing
yes
when does shape change of membrane occur
growth, division, endo/exocytosis
are membranes thick or thin
thin - essentially 2D
why is it good that membranes are thin
they enhance reaction rates
are membranes permeably
selectively permeable
can polar molecules pass through the membrane
they have a limited ability to pass through
what drives the formation of the membrane
hydrophobic effect
where are a majority of the glycolipids in the membrane
extracellular lumen
are glycolipids more on the cytosolic or lumen side
lumen
how do individual lipids orient in the bilayer
based on distribution of hydrophobic and hydrophilic character
what/were is lateral diffusion
within a leaflet
how fast is lateral diffusion + why
very rapid because interactions are non covalent and there is little barrier to motion
how fast is transverse diffusino
slow
what are the 3 stages of increasing temperatures in bilayers
gel phase –> liquid ordered state –> liquid disordered state
what is another name for the liquid ordered state
the liquid crystal state
how do they maintain fluidity in membranes
by altering membrane lipids (homeoviscous adaptation)
what is the protein-lipid composition myelin sheath and why
more fatty and glycolipids (lower polarity) because its an insulator for nerve signals
what is the protein-lipid composition inner mitochondrial membranes and why
high in protein cause of energy production OXPHOS, ETC
where are the carbohydrate aspects of glycoproteins/ glycolipids (where in the plasma membrane)
facing exterior to cell at the plasma membrane
where does synthesis of lipids carry out in eukaryotes
integral membrane proteins in ER in eukaryotes
where does synthesis of lipids carry out in prokaryotes
integral membrane proteins in plasma membrane in eukaryotes
what can happen with an appearance of specific lipids in other leaflets trigger
+ example
it can trigger other events
appearance of phosphatidylserine in outer leaflets triggers cell for engulfment/degradation
what does appearance of phosphatidylserine in outer leaflets trigger
engulfment/degradation
are membranes symetrical
no
are lipids distributed symmetrically in the membrane
no
how are lipids distributed in the membrane
asymmetrically
how are proteins distributed in the membrane
they all have the same orientation/directionality in the membrane (like all the same proteins in the same membrane would be pointing in the same direction, not like one is up and another is down)
where are most choline containing lipids in erythrocyte membranes
primarily in the outer leaflet
where are most sphingomyelin in erythrocyte membranes
primarily in the outer leaflet
where are most phosphatidylcholine lipids in erythrocyte membranes
primarily in the outer leaflet
which lipid should only be in the inner leaflet
phosphatidylserine primarily in the outer leaflet
what can changes in phospholipid distribution signal
signal or target cell for death
how fast is movement of lipids from one from one leaflet to another in bilayers
slow
how fast is movement of lipids from one from one leaflet to another in membranes
rapid
what do integral membrane proteins do for movement of lipids
help reduce the energy barrier for movement of lipids
what kind of proteins help reduce the energy barrier for movement of lipids
integral membrane proteins
what does lipid asymmetrical transport require
input of energy (active transport process)
what do flippases do
import lipids from outside the cell to inside the cell
what do floppases do
export lipids from interior of the cell to the exterior of the cell
what do scramblases do
passive transport to equalize concentrations between leaflets
is flippase active or passive (What kind)
primary active
is floppase active or passive (What kind)
primary active
is scramblases active or passive
passive transport
which flip or flop would deal with phosphatidylserine
flippase
which flip or flop would deal with phosphatidylethanolamine
flippase
which flip or flop would deal with phosphatidylcholine
floppase
which flip or flop would deal with phosphatidylsphingolipids
floppase
can proteins associated with the cytoskeleton diffuse laterally
maybe not
why can some proteins not be able to diffuse laterally
if theyre anchored/associated with the cytoskeleton
what are the 3 main types of membrane proteins
peripheral
lipid linked
integral
what are the integral membrane proteins
- lipid linked
- integral
are peripheral membrane proteins integral
no
are lipid linked membrane proteins integral
yes
how can you isolate/remove peripheral proteins
through moderate changes like pH and salt
how can glycosylated phosphoinositol linked proteins be removed from the membrane
through the action fo phospholipases (C or D)
are proteins or lipids more free to move in the membrane
lipids usually i think
how can you isolate/remove integral membrane proteins
using detergents or organic solvents to mimic the hydrophobic environment of the membrane
are integral or peripheral membrane proteins easier to isolate from the membrane
peripheral
how can you classify integral membrane proteins (2)
based on structural composition of transmembrane region
or
topology
what are 3 classifications on integral membrane proteins
whether the transmembrane region is
- single helices
- helical bundles
- beta barrels
what are 2 classifications for classifying membrane proteins based on topology
- how many times they pass the membrane
- where the N terminal is located
what is bitopic
when the proteins passes 1 time through the membrane
what is polytopic
when the protein passes multiple times through the membrane
what is monotopic + 2 examples
when the membrane proteins are found only associated with one side of the membrane
ex: peripheral and lipid anchored proteins
what do you call it when the N terminal is on the inside of the cell
cytosolic
what do you call it when the N terminal is on the outside of the cell
lumen or extracellular
what is a type 1 integral membrane protein
single transmembrane domain with C on interior (cytosolic) and N on exterior (lumen or extracellular)
what kind of transmembrane regions can be described as polytopic
helical bundles and beta barrels
what is a type 2 integral membrane protein
single transmembrane domain with N on interior (cytosolic) and C on exterior (lumen or extracellular)
how many amino acid residues per turn
3.6
how many angstroms per residue
5.4
what is glycoPhorin (where found)
eryhtyocyte protein
what is special about glycophorin
it is heavily modified with sialic acid derivativs
what does glycophorin associate as
a dimer in the membrane
where is the N terminal in glycophorin
extracellular
what type of integral membrane protein is glycophorin
type 1 bitopic membrane protein
what happens to the N terminal in glycophorin
it is glycosylated
what happens to the C terminal in glycophorin
nothing
which terminal of glycophorin is modified and how
N terminus is glycosylated
where is the C terminal in glycophorin
intracellular
what kind of transmembrane region crosses the membrane in glycophorin
a single alpha helix
what kind of residues are seen in the alpha helix in the membrane of glycophorin
hydrophobic
how does the asymmetry of glycophorin compare to other integral membrane proteins
similar, applicable to other ones
how many amino acids typically cross the membrane with integral membrane proteins
20
what kind of amino acids typically cross the membrane with integral membrane proteins
hydrophobic
which terminal of many intergral membrane proteins is modified and how
N terminus domain is glycosylated
which terminus of glycophorin is heavily modified with sialic acid derivatives
N terminus domain
why is it good for glycophorin to be heavily modified with sialic acid derivatives in erythrocytes
So with 2 erythrocytes close together will repel electrostatically, so this way they can flow easily in the blood stream
how many transmembrane helices in bacteriorhodopsin
7
how long are each helix in bacteriorhodopsin
around 20 aa long
what kind of structure is in bacteriorhodopsin
polytopic alpha-helical bundle
what are exposed protein domains similar to
structures resembling soluble globular proteins
what is the exterior like in transmembrane domains
hydrophobic (transmembrane so still in the membrane, not like exterior of the protein)
what is the interior like in transmembrane domains
hydrophilic residues clustered in the interior ion channel
what will the amino acids be like that are exposed to the exterior aqueous environment
polar
what can helical transmembrane domain be like
single pass or multi pass
how many amino acids are in transmembrane structures
usually 20
what kind of amino acids are in transmembrane structures
hydrophobic
how can you determine helical transmembrane structures
using a hydropathy plot
are helical transmembrane structures single pass or multo pass
either or
what can hydropathy plots be used for
detecting/predicting helical transmembrane structures
whats the positive inside rule
interior cytoplasmic loops are often enriched with arginine and lysine (cytoplasmic edge of transmembrane helices)
is it easy to determine the structure for integral membrane proteins
its challenging
what kind of environments are required for purification and correct folding (topology prediction)
hydrophobic
what is the hydropathy index
a scale that measures the relative hydrophobic and hydrophilic tendencies of a chemical group
what score would a region with lots of hydrophobic residues get
relatively high
what would a high hydropathy index score mean
there are lots of hydrophobic residues
what would a low hydropathy index score mean
not lots of hydrophobic residues
what score would a region with very few of hydrophobic residues get
relatively low
how thick is the membrane (angstroms)
around 30
what happens if theres multiple peaks in the hydropathy index
likely a polytopic strucutre
what are beta barrel transmembrane proteins (what type of topic)
multipass (polytopic)
how are beta barrel strands oriented
at angle relative to membrane (45 degrees)
what are the interiors of beta barrels like
polar
what # of antiparallel strands are in beta barrels + why
an even number so that like 1 and the last can pair, etc
what are amino acids that are exposed to aqueous environments like
polar
what are amino acids that are exposed to interior environments like
non polar
what is the amino acid pattern like with beta-barrel transmembrane proteins
alternating polar non-polar (some exposed to polar exterior and some exposed to hydrophobic lipid bilayer cause they go up and down in the strand)
do hydropathy plots detect transmembrane domains
why
no, because the strands are too short and they may not be exclusively hydrophobic (alternating)
which amino acids are near the interface in integral membrane proteins
Trp Tyr
which amino acid types are near the interior exposed loops in integral membrane proteins
positive
whats the positive inside rule (specific aa)
interior exposed loops of helical bundles are often enriched for arg lys his (cytoplasmic edge of transmembrane helices)
what kind of philicity for solvent exposed (non buried) surfaces in integral membrane proteins
hydrophilic
what kind of philicity for amino acids exposed to bilayer core in integral membrane proteins
hydrophobes
why are tyr and trp often found in the surface area of the integral membrane protein
theyre amphipathic, so their polar parts interact with the polar head groups (hydrogen bonding) of the lipid, and the hydrophobic portions of the amino acid are
where are most charged residues in integral membrane proteins
almost exclusively on the surface/solvent exposed portions
what do lipid anchors do (2 things)
anchor proteins to membranes
may also target proteins to specific membrane locations
what are the types of lipid anchors
fatty acid, prenyl group or GPI linkage
what are prenyl anchors
isoprene based structures
what are 2 types of prenyl anchor residues
farnesyl residues and geranylgeranyl residues
what is the sequence that prenyl anchors are most commonly added to
C-X-X-Y
X=aliphatic aa
Y=specificity
how does prenyl anchor adding work
sequence C-terminal to Cys removed (irreversible), then a thioether to C-terminal Cys
which amino acid determines specificity of prenyl anchors
the Y in the sequence C-X-X-Y (terminal amino acid)
is prenyl anchor reversible
no
what is removed when prenyl anchors are added
sequence C-terminal to cys
which terminal is modified with prenyl anchors
C
when does prenylation occur and why
post translational because you need the C terminal to be made
which direction are proteins synthesized
N to C
what are 2 types of lipid-linked proteins
palmitoylation
myristoylation
what is palmitoylation (what becomes attached)
16:0 fatty acid
what is myristoylation (what becomes attached)
14:0 fatty acid
what kind of linkage happens with palmitoylation
thioester linkage to cys or ester linkage to ser to the fatty acid
what kind of linkage happens with myristoylation
amide linkage (from fatty acid and N terminus)
is myristoylation reversible
no
is palmitoylation reversible
yes
is palmitoylation or myristoylation reversible
palmitoylation
is palmitoylation or myristoylation irreversible
myristoylation
when does myristoylation occur (translation)
why
co or post
its a mod on the N terminal end
when does palmitoylation occur (translation)
why
post because its an internal polypeptide modification
where does palmitoylation and myristoylation occur (where in membrane)
on the inside/ inner face of plasma membrane
which lipid linked membrane protein happens in the middle
palmitoylation
which lipid linked membrane protein happens on the N terminus
myristoylation
which lipid linked membrane protein happens on the C terminus
prenylation
which lipid linked membrane protein has 16 fatty acid
palmitoylation
which lipid linked membrane protein has 14 fatty acid
myristoylation
what are GPI anchors (what do they stand for)
glycosylated derivative of phosphatidyl inositol
where do GPI anchors do
on outer face of plasma membrane
what kind of modification happens with GPI anchors + why
post translational modification
bc as C terimus
where in the peptide chain do GPI anchors occur
C terminus
what can happen to GPI anchors and why
they can be cleaved by phospholipases as part of regulation
