VL10: Bacterial secretion systems Flashcards
How is protein localization and timing important?
proteins must get to the right place at the right time
e. g.periplasmic enyzmes need to get to periplasm
e. g.virulence factors have to be secreted at the right n´time
How many secretion system types exist, and where are they located?
7
T1,3,4,6SS transport in a single step through IM,OM
T2,5SS transport via Sec or Tat over IM, then separate step overOM
T3,4,6SS transport over host membranes
T7SS only in Mycobacteria
What is the most important secretion system? What are they used for?
Sec (and Tat)
homologues in all domains of life
system was used to traffic proteins to extracellular locations in a primitive (early) organism
used to assemble components of other secretion szstems (e.g.T3SS)
Tat is not found in mammals
How does the Sec system work? Which components are implemented?
- co translational translocation (Sec)
- post-traslation translocation of unfolded proteins by Sec-translocase
- Translocation of folded proteins by Tat translocase
Sec secretes unfolded proteins, requires N-terminal signal peptide
a) Secretory proteins are posttranslationally targeted to secA with their signal sequence (sometimes with chaperone secB)
b) Membrane proteins or hydrophobic preproteins are targeted to the Sec translocase by the SRP bound to the ribosome
c) Some membrane proteins are inserted into the cytoplasmic membrane via YidC
SecA motor protein
most proteins are exported with Sec
membrane proteins
many virulence factos
How does the Tat pathway work?
Twin argenine signal peptides translocation
TatA protein translocon
TatB and TatC protein recognition
N-terminal signal peptide includes 2 arginines
translocates folded prot
PMF
signal cleaves after translocation
What are characteristics of the type 1 secretion system? examples
single step over IM, OM
consists of ABC, MFP, OMP
(ATP binding casette, recogniyes substrate and secretion signal, Membrane fusion protein, link between IM and OM, Outer membrane protein, barrel in OM)
secretes toxins, proteases, lipases
What is ABC?
ABC transporters are transmembrane proteins, use energy of ATP hydrolysis to drive translocation of substrates across membranes
Compare type 1 secretion to tripartite drug efflux
structurally similar
drug-efflux pumps account for more than 10% of all transporters
What are the characteristics of type 3 secretion system??
- injectisome
- direct in jection of virulence factors from cytoplasm into hostcells
- Structure/evolution related to bacterial flagella
- needle terminates with tip structure that helps form the translocation pore in human cell
What other structure are type 3 secretion systems homologous to?
Structure/evolution related to bacterial flagella
Give some examples of type 3 secretion in animal pathogens
Cytoskeletal rearrangements
Intracellular growth
Inhibition of phagocytosis
Invasion of epithelial cells
Uptake of Shigella, Salmonella
Prevents phagocytosis of Pseudomonas aeruginos and Yersinia
Describe the type 4 secretion system
like T3SS directlz into host cells
can transport DNA and protein
share ancestry with conjugation system
Briefly describe 3 roles of type 4 secretion in bacteria
a) conjugative: delivers plasmids or transposons from donor to recipient
b) DNA uptake and release: exchange of DNA with milieu
c) Effector translocation: delivers DNA or protein substrates to eukaryotic cells (virulence)
How does Legionella pneumophilia survive intracellularly?
T4SS injects effector prot into host cell (macrophages)
effectors hijack cargo vesicles and transform phagosome into speciualied membrane that resembles ER-> no lysosomal fusion, L.pneumophilia can replicate until lysis
What is CagA and what does it do?
Helicobacter pylori injects CagA with T4SS into host cell -> CagA activates/inactivates multiple signal proteins -> cancer development
