Secretion Systems Flashcards
(19 cards)
Sec Pathway signal
‘n-region’: Positive N-terminal region
Hydrophobic core
Cleavage site: Ala-X-Ala
Sec pathway
Recognised by SecB (cytoplasmic chaperone)
Transported to SecA, which interacts with SecYEG
Cycles of ATP hydrolysis by SecA drive translocation through SecYEG translocon
SRP-like pathway
SRP recognises signal sequence
Docks on FtsY, transports through SecYEG
Usually for IM-embedded protein
Tat pathway signal sequence and folding
Twin Arg-motif in ‘n’-region but otherwise same architecture
Translocates in folded state
Chaperone-mediated proofreading:
Bound by chaperone, which masks twin Arg motif.
Insertion of cofactor displaces chaperone
Tat pathway translocation
Twin Arg recognised by TatC within TatBC complex
Recruits TatA protomers that polymerises, forming a pore
Translocates in H+-dependent manner
T1SS
Double-membrane spanning tripartite
IMC is a ABC (ATP hydrolysis), recognises C-TERMINUS of cargo. Secretion signal not removed
MFP - periplasmic adaptor
TolC - trimeric OM protein that forms a B-barrel, with a-helices that interact with MFP
Eg. haemolysin in E. coli, HasA for haem acquisition
RND efflux pumps
closely related to T1SS - removes small toxic exogenous molecules
Couples protein transport to PMF
CryoEM structure of AcrB-AcrA-TolC was obtained
T2SS - examples and mechanism
Pseudolysin of P. aeruginosa, Cholera toxin for Vibrio cholera
Two-step mechanism with periplasmic intermediate
T2SS structure
OM formed of oligomeric GspD of secretin family
GspS is a periplasmic chaperone that facilitates assembly of GspD in an OM complex
Pseudopilus of GspGHIJ - remains confined within periplasm
Pseudopilins inserted into IM by SecYEG translocon - GspO, an N-MePhe peptidase, cleaves and methylates -terminal Phe residue)
GspE is a cytoplasmic ATPase that associates with GspL in the IM, uses ATP hydrolysis to promote assembly of pseudopilin subunits
Mechanism of T2SS
- Export to periplasm - Sec or Tat
- Cleavage of signal peptide and folding in periplasm (eg. cholera toxin S-S bridge formation via DsbA)
- Unknown secretion signal but signal patch motif can arise from periplasmic folding
- Secretion across OM is mediated by assembly of periplasmic pseudipilus - acts as a piston to push protein through GspD in the OM, driven by ATP hydrolysis by GspE
T3SS
Injectisome; Double-membrane spanning; No free periplasmic intermediate
Delivers effector proteins into cytoplasm or PM of target Euk cells
Genes that encode T3SS sometimes in Pathogenecity islands (eg. SPI-1)
Evolutionarily related to Flagellar assembly genes
Eg. Yops
T3SS machinery
Injectisome:
OM protein comprises secretins that have homology to GspD
Cytoplasmic ATPase
Secretion signal in N-terminus;
T4SS - examples
Translocate DNA or Proteins into Euk or Bacterial target cells
Eg. T-DNA targeting in Argobacterium
Pertussis toxin in B. Pertussis
CagA in H. pylori
Plasmid conjugation
T4SS machinery
Double membrane-spanning - no free periplasmic intermediate
2 components have traffic ATPase characteristics in cytoplasmic face
Type IV needle used to deliver protein/DNA into target cell
T5SS
Two-step process, autotransporter
Loses both C-terminal region and N-terminal region
Eg. IgA protease of Neisseria gonorrhoeae
Secretion Machinery of T5SS
N-terminal signal sequence mediates export via SecYEG translocon
Cleaved at IM by signal peptidase, releasing mature protein in periplasm
BAM complex mediates insertion of C-terminal domain into OM, forming B-barrel, enabling translocation of the rest of the protein through the pore
Autoproteolysed or membrane protease cleaves - releases mature protein
Two-partner systems Type Va
Type Va
Both partners secreted via Sec pathway, N-terminal sequence cleaved off
One partner inserts into OM as a B-barrel, the other translocates through the pore
Eg. filamentous haemmaglutinin of bordetella
T6SS
Injects toxic effector proteins into euk and prok cells
Pathogenesis and bacterial competition
IM complex comprises IM proteins homologous to T4SS
Tail complex has components that shares structural homology to phage tails, with similar contraction mechanism
T6SS mechanism
DMSS
Tail complex assembles into IM complex, recruits effector proteins
Sheath contraction leads to ejection of spike-tube complex across target membrane, delivering effectors
Cytoplasmic ATPase disassembles contracted sheath, enabling reassembly of a new T6SS
