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LETS LEARN MORE ABOUT ENDOPLASMIC
RETICULUM...
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THREE WAYS IN WHICH SINGLE PASS
TRANSMEMBRANE PROTEINS CAN BE INSERTED
INTO THE ER:
(1) Simplest case: an amino-
terminal signal peptide initiates
translocation, just as for a solubleprotein., but an additional
hydrophobic segment in the
polypeptide chain stops thetransfer process before the entire
polypeptide chain is translocated.
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Stop transfer peptide- anchors the
protein in the membrane after theER signal peptide is released from
the translocator and is cleaved off.Forms a single alpha-helical
membrane-spanning segment, with
the amino temrinus of the protein onthe luminal side of the membrane
and the carboxyl terminus on the
cytosolic side.
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(2,3) In the other 2 cases:
The signal peptide is internal, rather
than at the terminal end of the protein.
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MULTIPASS TRANSMEMBRANE PROTEINS:
the polypeptide chain passes back and forth
repeatedly across the lipid bilayer.
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TRANSLOCATED POLYPEPTIDE CHAINS FOLD
AND ASSEMBLE IN THE LUMEN OF THE ROUGH
ER:
ER Resident proteins
Contain an ER retention signal of four
amino acids at their carboxyl terminus that
is responsible for retaining the protein in
the ER.
Some of these proteins function as
catalysts that help many proteins that are
translocated into the ER to fold and
assemble correctly.
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EXAMPLE OF ER RESIDENT PROTEINS:
(1) Protein disulfide isomerase
Catalyzes the oxidation of the free
sulfhydryl (SH) groups to form
disulfide bonds.
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EXAMPLES...
(2) Binding protein (BiP)
Chaperone protein that is structurally
related to hsp70 proteins and, likethem, recognizes incorrectly folded
proteins, as well as protein subunits
that have not yet assembled into theirfinal oligomeric complexes.
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SOME MEMBRANE PROTEINS EXCHANGE A
CARBOXYL-TERMINAL TRANSMEMBRANE TAIL
FOR A COVALENTLY ATTACHEDGLYCOSYLPHOSPHATIDYLINOSITOL (GPI) AFTER
ENTRY INTO THE ER
Glycosylphosphatidylinositol (GPI)
Contains two fatty acids.
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MOST MEMBRANE LIPID BILAYERS ARE
ASSEMBLED IN THE ER
The ER membrane produces nearly all of the
lipids required for the elaboration of new cell
membranes, including both phospholipids
and cholesterol.The major phospholipid made is
phosphatidylcholine (or lecithin), which can be
formed in three steps from choline, two fattyacids, and glycerol phosphate.
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2 OTHER MAJOR MEMBRANE PHOSPHOLIPIDS
Phosphatidylethanolamine (PE) and
Phosphatidylserine (PS) as well as the
minor phospholipid Phosphatidylinositol(PI), are synthesized in the same
manner as that of the lecithin.
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Aside from producing phospholipids, the ERalso produces cholesterol and ceramide.
Ceramide made by condensing the amino
acid serine with a fatty acid to form the amino
alcohol sphigosine; a second fatty acid is the
added to form ceramide.
transported to the GA, where it serves as
the precursor for the synthesis of two types
of lipids: oligosaccharide chains are added to
form
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glycosphingolipids, and phosphocholine head
groups are transferred from phosphatidylcholine
to other ceramide molecules to form
sphingomyelin.
Both glycosphingolipids and sphingomyelin are produced
relatively late in the process of membrane synthesis. Because both are produced by enzymes exposed to the
GA, they are exclusively found in the noncytosolic half of the
lipid bilayers that contain them in contrast to the
phospholipid synthesis which occurs in the cytosolic half of
the lipid bilayer.
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Recall that the plasma membrane and themembranes of the Golgi apparatus,lysosomes, and endosomes all form part of a
membrane system that communicates withthe ER by means of transport vesicles thattransfer both proteins and lipids.
Mitochondria, plastids and peroxisomes arenot included since they require differentmechanisms.
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PHOSPHOLIPID EXCHANGE PROTEINS
Also called phospholipid transfer proteins.
Shown in vitro to have the ability to transferindividual phospholipid molecules between
membranes. functions by "extracting" a molecule of the
appropriate phospholipid from a membrane
and diffusing away with the lipid buried withinits binding site.
Recognizes only specific types of proteins.
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PROTEIN EXCHANGE PROTEINS...
Act to distribute phospholipids at randomamong all membranes present.
In principle, a random exchange process can
result in a net transport of lipids from a lipid-rich to a lipid-poor membrane, allowingphosphatidylcholine and phosphatidylserinemolecules, for example to be transferredfrom the ER where they are synthesized, to amitochondrial or peroxisomal membrane.
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THE END!
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