Protein Trafficking Flashcards
Where does protein synthesis occur?
Where could the proteins be transferred to?
Nuclear-encoded proteins begin synthesis in the cytosol.
From the cytosol they can be transported to:
nucleus, mitochondria, ER, chloroplast, peroxisomes, etc.
How does a protein know where to go in the cell?
SORTING SIGNALS
signal sequence OR signal patch
What are signal sequences?
exposed, single stretch of amino acids, often at the end of the polypeptide chain (N-terminus)
these can be cleaved/uncleaved after targeting
What are signal patches?
amino acids contributing to the signal are separate until after the protein folds
List some examples of signal sequences.
NUCLEAR IMPORT
lysine and arginine-rich sequences
MITOCHONDRIAL IMPORT
amphipathic alpha helix
ER IMPORT
hydrophobic amino acids
How does a protein (a large macromolecule) cross the lipid bilayer?
PROTEIN TRANSPORT
Proteins have a signal sequence which sticks out at the end. There are receptors that recognise this signal on the membrane which act as a channel through which to guide the protein.
Where do all nuclear-encoded proteins begin synthesis?
In the cytosol
What are the channels by which proteins enter the NUCLEUS from the cytosol?
NUCLEAR PORES
Nuclear pores are made up of nucleoporins
Small molecules (<5000 daltons) freely diffuse through nuclear pores
What state must proteins be in to enter or leave the nucleus?
Proteins transported are post-translational (folded proteins)
Describe the mechanism by which proteins are IMPORTED into the NUCLEUS.
CHANNEL — nuclear pore
RECEPTORS — nuclear import receptors
SIGNAL — nuclear localisation signals
NLS on the protein binds to IMPORTIN (nuclear import receptor) which binds to a nucleoporin binding site on the nuclear pore
Describe the mechanism by which proteins are EXPORTED into the NUCLEUS.
CHANNEL — nuclear pore
RECEPTORS — nuclear export receptors
SIGNAL — export signal
Export signal on the protein binds to EXPORTIN (nuclear export receptor) which binds to a nucleoporin binding site on the nuclear pore
What type of substance are Importin and Exportin?
Karyopherins
What is Ran-GTPase? What does it do?
Ran-GTPase is a ???
What is meant by translocation?
The transport of a protein across a membrane.
What is meant by TOM and TIM?
TOM — Translocon of the Outer Membrane
TIM — Translocon of the Inner Membrane
Describe the mechanism by which proteins are IMPORTED into the MITOCHONDRIA.
CHANNEL — TOM and TIM complexes
RECEPTORS — TOM complex
The signal sequence of the post-translational unfolded protein is recognized by a receptor protein in the TOM complex. The protein is then translocated through the TOM complex and transferred to the TIM complex.
What are the energy requirements for protein import into the mitochondria?
ATP
Electrochemical gradient across the inner membrane
What happens to a protein once it has been imported into the mitochondrial matrix?
The protein is cleaved by SIGNAL PEPTIDASE, producing a mature mitochondrial protein.
How is the unfolded protein kept unfolded during translocation?
The protein binds cytosolic Hsp70
Define “nascent” in the context of proteins.
A nascent polypeptide chain is one which is newly synthesized
Define “glycosylation”
Glycosylation refers to the addition of sugars to a protein or lipid
Describe the process of co-translational import of proteins into the endoplasmic reticulum (ER)
CHANNEL — Sec61 complex
RECEPTORS — SRP receptor
SIGNAL — SRP (signal recognition particle)
SRP binds to the signal sequence on the protein, causing translation to pause. The SRP-bound ribosome attaches to the SRP receptor on the ER membrane.
The protein remains attached to the translocon on the ER membrane, translation resumes and translocation begins.
SRP and the SRP receptor are displaced and recycled.
What role does GTP hydrolysis play in protein translocation into the ER?
GTP hydrolysis powers assembly of the nascent chain — translocon complex, as well as release of the SRP / SRP receptor
What are the two types of protein import into the ER?
Co-translational and Post-translational
