Protein targeting and protein degradation Flashcards
preprotein (proteolytic processing)
- protein precursor that contains a signal pepetide sequence that is cleaved
- longer ones are more commonly removed because they can affect folding
- occurs in ER
signal anchor sequences
- signal sequences that are rich in hydrophobic amino acid residues to help anchor transmembrane proteins
Nuclear Localization sequences
- short sequences in proteins destined for the nucleus
- do not get cleaved
proprotein
- proteins initially synthesized as large precursor proteins and need to be proteolytically trimmed to become active
what is the difference between a preprotein and a proprotein
- preproteins have a signal sequence that needs to be cleaved
- proproteins are inactive until modification (usually cleavage) activates them
- cleavage occurs in the ER
What types of proteins are targeted to the ER?
- membrane proteins
- secreted proteins
- lysosomal proteins
- proteins that need posttranslational modification
- removal of signal sequences, glycosylation (mostly N-linked)
- nuclear, mitochondrial, and chloroplast proteins do not go through the ER
Explain how ER targeting works
- a signal recognition particle (SRP) binds the emergent signal sequence and the ribosome
- SRP binds GTP which pauses elongation
- ribosome/SRP complex binds to receptors on the face of the ER
SRP hydrolyzes and GTP dissociate - translation resumes
- signal sequence is cleaved and full protein is translocated into the ER
how does glycosylation affect a protein?
- can change polarity and solubility (carbohydrates are polar)
- serve as marker protein
- structural complextiy
- facilitate cell-cell interactions
location of N-linked vs O-linked glycosylation
- N-linked occurs in the ER
- O-linked occurs in the golgi
how does N-linked glycoslyation work?
- it is done by transferase only found in the lumen of the ER
- oligosaccharide core transferred to the protein
- core can be modified in different ways for different proteins
How does golgi sorting work
After proteins leave the ER, do they go directly to their final destination? If not, where do they go and what happens to proteins there?
- no, they go to the golgi to get sorted
- golgi sends them to their final destination
what do rab proteins do?
- they are recruited to the vesicle and interact specifically with particular acceptor compartment membranes
- rab proteins on the vesicle are recognized by specific tethering proteins on the acceptor
what do SNARE proteins do?
- v-SNARE on vesicle and t-SNARE on acceptor recognize each other
- triggers membrane fusion
4 steps of protein transport
- budding
- transport
- docking
- fusion
what does importin do
- binds proteins with NLS and aids them through nuclear pores
- gets recycled back out once done by other protein (Ran-GTP)
two types of protein degradation
lysosome degradation
- relatively nonspecific
- degrades proteins with longer half lives, membrane proteins, and misfolded proteins
- doesn’t occur in prokaryotes
proteasome degredation
- ATP dependent
- degrades proteins that have been covalently linked to poly-ubiquitin
what is ubiquitination and what is its purpose
- attachemnt of one or more ubiquitin
- ubiquitin is a highly conserved protein in eukaryotes
- most common effect is labeling proteins for proteasomal degradation
what does the proteasome do
- degrades proteins with K48 ubiquidation
two subcomplexes of the proteasome
- core particle
- protease activity - regulatory particles
- recognition of ubiquitin chain
- has ATPases that likely function in protein unfolding and translocation into the core
- de-ubiquitination
what happens if there is a defect in ubiquitin-dependent proteolysis
- no way to degrade cell cycle proteins
- improper degradation of tumor suppressor proteins can lead to cancer
- diseases such as cystic fibrosis, liddle’s syndrom, Alzheimers, parkinsons, and huntingtons diease
