Membrane Compartments and Membrane Protein Sorting Flashcards
(40 cards)
The precise sorting of macromolecules within cells results in multiple membrane enclosed compartments with discrete functions. How is this accomplished?
sorting signals (consisting of specific amino acid sequences that form a signal peptide) in proteins that direct their cellular localization. NOTE: those proteins lacking specific organelle sorting signals will remain in the cytosol
Protein synthesis in the cytosol occurs where?
free ribosomes
Proteins made on free ribosomes are destined to be transported where?
Proteins may either remain in the cytoplasm (these lack sorting signals) or can move into the nucleus, peroxisomes or mitochondria.
What is the fate of proteins synthesized on the rough endoplasmic reticulum (ER)?
these proteins will either remain in the ER or undergo sorting to the Golgi, lysosomes, secretory vesicles or plasma membrane.
What are the three mechanisms for moving proteins between cellular compartments?
- Gated transport (movement from cytosol to the nucleus)
- Transmembrane transport (movement from the cytosol into mitochondria, peroxisome and ER)
- Vesicular transport (movement through the Golgi and movement to lysosomes, secretory vesicles, plasma membrane)
Nuclear pore complexes are the ‘gates’ to the nucleus. What is the name of the proteins that compose these gates?
nucleoporins (mediate bi-directional transport
through a water filled channel)
How do nuclear pore complexes allow the transport of small molecules to the nucleus?
aqueous channels in the complex
Nuclear pore complexes allow large molecules to enter and exit the nucleus only if they are attached to what?
nuclear localization signals or nuclear export signals (NOTE: large molecules typically do so in the folded state)
Nuclear localization signals are composed of what?
one or two short stretches of positively charged amino acids
The outer membrane of the nucleus is continuous with which organelle?
ER
The inner membrane of the nucleus contains sites for binding of which structures?
chromatin and the nuclear lamina
Are proteins typically fully folded when transporting through a nuclear pore?
Yes
Nuclear localization signals on proteins bind to nuclear import receptors which in turn bind to which structure of the nuclear pore to guide protein transport into the nucleus?
cytoplasmic fibrils of nuclear pores
Describe how nuclear transport of large molecules (i.e. proteins and mRNA) is an energy driven event.
Following transport into the nucleus, the nuclear transport receptor and cargo bind to “Ran-GTP”, which stimulates the release of the cargo (in this process, Ran-GTP physically displaces the cargo and forms a complex with the nuclear transport receptor). The transport receptor (still bound to Ran-GTP) then migrates to cytosol where Ran-GTP is hydrolyzed to Ran-GDP, which causes it to release from the receptor. Then, the nuclear transport receptor is free to bind another cargo+nuclear signal complex and repeat the cycle.
Describe protein transport to mitochondria.
- Proteins synthesized in the cytoplasm which are destined for the mitochondria have a signal peptide specific for the mitochondria at the N-terminus (often called a matrix targeting sequence) and are imported post-translationally in an unfolded state.
a. All proteins imported into the mitochondria have at minimum a matrix targeting sequence (contains positively charged residues and forms an amphipathic helix)
b. Cytosolic and mitochondrial chaperones maintain the protein in its unfolded state during transport
c. Unfolded protein binds a receptor in the outer membrane. This complex diffuses (i.e. slides along the outside of the outer membrane) in the membrane until it encounters a translocation channel on the surface. The protein is then transported through the channel all the way to the matrix (i.e. the channel spans both membranes).
d. The signal peptide is cleaved off the protein in the matrix by a signal peptidase to form a ‘mature protein”
e. Some proteins never make it all the way into the matrix but rather a second signal peptide anchors them into the inner membrane
Are proteins that are synthesized in the cytosol and transported to mitochondria in a folded or unfolded state during transport? Is this pre- or post-translation?
unfolded; post-translation
The matrix targeting sequence of proteins bound for mitochondria form what structure?
amphipathic helix (i.e. helix is charged on one side and uncharged on the other side)
what is the role of cristae in mitochondria?
cristae are convoluted foldings of the inner membrane which greatly expand its surface area, enhancing the ability to make ATP.
What maintains the protein in its unfolded state during transport to mitochondria?
Cytosolic and mitochondrial chaperones
Mitochondrial proteins destined for the inter-membrane space or the mitochondrial inner membrane require two signal sequences. How does this work?
These proteins move into the matrix via conventional mitochondrial transport where their matrix-targeting sequence is cleaved and then a second signal peptide is exposed that targets them to the inner membrane or the inter-membrane space.
Alcohol dehydrogenase is found where in the mitochondria?
in the matrix (i.e. it does not possess a secondary signal peptide)
Peroxisomes are most abundant where in the body?
liver and kidney cells (NOTE: they are still found in all cells in the body)
What are the main functions of peroxisomes? (Hint: 3 things)
- A role in detoxification of toxins, particularly in liver and kidney cells.
* half the ethanol we drink is oxidized in peroxisomes - Breakdown of fatty acids via oxidation (especially long chain FAs)
- Site of synthesis of some lipids
a. In animal cells a second site of synthesis (besides ER) of cholesterol
How do peroxisomes facilitate the breakdown of fatty acids?
oxidative reactions (NOTE: this also occurs in the mitochondria but fatty acids >20 carbons occurs only in peroxisomes)
