20 terms

Quiz 5: Post-Translational Modifications-ER Tranport

What are acylation and prenylation?
Covalent, post-translational modifications...
What is acetylation (of histones and other proteins)?
Covalent, post-translational modifications that put an acetyl group on lysine residues of histones to increase gene expression.
What are the 3 main types of membrane anchors for proteins on the cytosolic side of the bilayer?
Myristoyl, Palmitoyl, and Farnesyl anchors.
How does a Myristoyl anchor work?
It is a single FA attached via an amide linkage to the terminal amino group of a protein. It is a weak anchor, thus is used as a reversible signal in the cytosol.
How does a palmitoyl anchor work?
It is a single FA attached via a thioester linkage between a (specific) cysteine group on the protein that is surrounded by sequences that target it for palmitoylation. Reversible linkage.
How does farnesyl anchor work?
It is a isoprenyl group (farnesyl or geranylgeranyl - building blocks of cholesterol)) via a thioether linkage and the C-terminus on the protein. Linkage is permanent, but protein can be reversibly inserted or removed from the membrane. (E.g. Ras)
How do most transmembrane proteins work?
Via α-helicies that span the bilayer (though you can get some β-sheets that span it).
Where are most mitochodrial proteins synthesized?
In cytosolic ribosomes from NUCLEAR DNA.
How do cytosolic proteins get into the mitochodria?
They have a mitochondrial import signaling sequence (α-helix with positive charged residues on one side) that is recognized by receptors on the mito outer membrane. Then they are unfolded with the help of Hsp70 chaperones and threaded through the membrane. (Same signal can be recognized by TIM complex on inner mito membrane for import into matrix.)
What is the role of Hsp70 in mitochondrial import of proteins?
Clamp on end of entering protein inside, preventing it from leaving out, and as a thermal ratchet. Can then help to refold it.
Which organelles have import sequences?
Nucleus (also has export sequence), mitochondria, peroxisomes, ER.
When does transport of proteins into the ER mostly happen?
Co-translationally. Free ribosomes associate with proteins on ER surface.
How does the SRP cycle work?
A protein being synthesized by free ribosome produces ER signal sequence. This part sticking out is recognized by the Signal Recognition Particle (SRP), which binds and pauses translation. SRP receptor on ER binds and hands off to translocon detaching SRP & receptor to dissociate continuing synthesis.
What is Sec61?
ER translocator complex (the one with the movable plug).
Which end of a ER translocated protein goes in first?
N-terminus, because that's what was synhtesized first (for either tranmembrane proteins or those just transferred to the ER).
How is a Type II membrane protein inserted?
Either co- or post-translationally. A "start-transfer" sequence in the middle of the protein is recognized and treaded through. In this way the C-terminus can be on the ER lumen side.
What is Zellweger Syndrome?
A defect in the import mechanism of peroxisomes. Usually fatl by age 6.
What is dolichol and what does it do?
It's an isoprene-derived molecule that serves as a sugar donor for transmembrane proteins. Usually transferred to an Asn residue on the protein.
Where is the dolichol glycosylated?
First on the cytosol side, but then flipped to the lumen side of the ER.
What can be done with GPI anchors?
ER transmembrane proteins can be transferred to a Glycosylphosphatidylinositol anchor on the inner membrane of the ER held by the FA chains of the GPI. It can then be extocytosed to the plasma membrane subject to enzyme activity. (Tryponosomes use this to evade the immune system.) Prions are GPI-anchored proteins.