11. Targeting and Modifying Proteins Flashcards
When do ribosomes remain cytosolic?
When proteins are destined for cytosolic or post translational import into organelles.
What four things are required for protein sorting?
A signal, a receptor to recognise the signal and direct it to the correct membrane, a translocation machinery (transports it across the membrane) and energy for transferring the protein to the new place.
For proteins targeted for the ER lumen, where are their usual signal locations? Are their signals removed? What is the type of signal?
Signal location on N-terminus. The signal is removed. The signal is 6-12 hydrophobic amino acids often preceded by 1 or more basic amino acids.
For proteins targeted for the mitochondrial matrix, where are their usual signal locations? Are their signals removed? What is the type of signal?
N-terminus. The signal is removed. The nature of the signal is an amphipathic helix 20-50 residues with R/K and hydrophobic sides.
For proteins targeted for the peroxisome, where are their usual signal locations? Are their signals removed? What is the type of signal?
C-terminus. The signal is not removed. The nature of the signal is usually a S-K-L at the C-terminus.
For proteins targeted for the nucleus, where are their usual signal locations? Are their signals removed? What is the type of signal?
The location is internal. The signal is not removed. The nature of the signal is one cluster of 5 basic amino acids or 2 smaller basic clusters separated by around 10 amino acids.
What happens when a protein imports into the mitochondrial matrix?
Chaperones keep the protein with signal unfolded. The signal binds to the receptor and the protein is fed through a pore in the outer membrane of the mitochondria. The protein moves through the channel in adjacent inner membrane. The signal is cleaved.
What happens when a protein imports into the nucleus?
In the cytosol, importin binds to the cargo containing the nuclear localisation signal. The Ran-GTP binds to importin and there is a conformational change that displaces the cargo. The importin with bound Ran-GTP is recycled to the cytoplasm.
What can mutation of nuclear localisation signal cause?
Swyer syndrome. Loss or mutation of NLS in sex determining region Y protein. They have an XY genotype but outwardly appear female.
Leri-Weill dyschondrosteosis and Langer mesomelic dysplasia. R173C mutation in NLS of SHOX transcription factor. Short stature as SHOX is needed for skeletal development.
What happens when proteins import to the peroxisomal matrix?
The import receptor binds cargo with PTS. Peroxisomal protein remains folded and the receptor integrates into the translocon and opens it. The PTS dissociates from the receptor and returns to cytosol, this requires ATP hydrolysis.
What can be a consequence of mutation in peroxisomal enzymes?
Rhizomelic Chondrodysplasia Punctata. Mutation in Pex7 leads to shortened limbs and mental retardation.
What happens to proteins targeted to the ER/ secretory pathway?
The proteins are synthesised on bound ribosomes, and are transported across the ER membrane. ER buds and fuses with Golgi, there is some Golgi to ER retrograde transport. There is cisternal progression, and retrograde transport from later to earlier Golgi cisternae. They’re then secreted.
What are the two types of secretion from cells?
Constitutive secretion and regulated secretion (endocrine secreting hormones, exocrine secreting digestive juices and neurocrine secreting neurotransmitters).
Which surface are proteins secreted from the pancreatic cells?
The apical surface.
How are secretory proteins synthesised and trans located across the ER membrane?
The ribosome synthesises the protein in the cytoplasm.
He signal sequences is recognised by the signal recognising particle. The SRP receptor is present in the ER membrane.
The alpha subunit of the receptor gets GTP bound and has higher affinity for the ribosome.
The translocon opens.
Signal peptidase cleaves the signal sequence and the protein is delivered.
The channel closes and the ribosome is dissociated for recycling.
