Molecular Basis of Bacterial Infections Evelien Floor
Bacterial secretion systems
Introduction to secretion systems
Bacteria have to interact with their environment to survive and use secretion systems for this.
Protein secretion systems are involved in nutrient scavenging, motility, adhesion, host cell invasion
and escape, waste release and assembly. The secretion system is used for assembly of membranes,
membrane proteins and the cell wall. Assembly of surface structures:
Adhesins
Invasins
Fibrils
Fimbriae or pili
Conjugative pili
Flagella
Almost 20% of all bacterial proteins are secreted. Membranes are impermeable for proteins, and
proteins are made inside the cytosol. Therefore, a couple of steps are required:
Targeting
o Presence of a signal for secretion
Membrane crossing (twice in Gram-negatives)
o When only one membrane is crossed it is still called secretion
Processing
o Cleavage of the signal for secretion
Correct folding after (and not before) secretion
Gram-negative bacteria need different mechanisms for secretion compared to Gram-positive
bacteria because of the differences in membrane composition. Gram-negative bacteria consist of a
much wider range of secretion systems than Gram-positive bacteria. An efficient and effective
protein secretion requires different secretion mechanisms. Currently there are 7 known secretion
systems.
Common features of secretion systems
Secretion of a protein starts with the ribosome that synthesizes a protein with or without a signal
peptide. Proteins with a signal peptide will eventually be secreted. The secretion system consists of a
protein complex that mediates protein translocation. Assembly of secretion system and secretion of
their substrates (proteins) is usually regulated. Protein secretion is an active process: it consumes
energy (ATP, proton motive force).
1
, Molecular Basis of Bacterial Infections Evelien Floor
Every signal peptide consists of a positively charged N-terminus followed by a hydrophobic site and a
cleavage site. Signal peptidase is responsible for cleavage, if cleavage is absent the protein will
remain in the plasma membrane. Functions of the signal peptide:
Keep the protein unfolded
Targeting to the membrane (translocon)
Insertion hydrophobic (H) domain into the membrane
Secretion across the cytoplasmic membrane
Two main proteins are responsible for secretion across the cytoplasmic membrane: Sec and Tat. Sec
secretes unfolded proteins while Tat secretes folded proteins. Sec is also able to insert membrane
proteins into the inner membrane.
Sec
Sec is the general secretion pathway (GSP) present in all organisms. Most secretory proteins use this
system. Sec also mediates integration of membrane proteins and is involved in assembly of its own
and other secretion complexes.
Sec secretion is possible co-translationally or post-translationally. Co-translational: SRP recognizes
the signal peptide and pushes the protein through the secYEG channel while the ribosome is still
synthesizing the protein. Post-translational secretion can be chaperone-dependent or chaperone-
independent. Post-translational chaperone-dependent: SecA or SecB keep the protein unfolded and
transport the protein to SecYEG. Post-translational chaperone-independent: proteins stay unfolded
in the cytosol without the use of chaperones. Lep is the signal peptidase in E. coli
2
Bacterial secretion systems
Introduction to secretion systems
Bacteria have to interact with their environment to survive and use secretion systems for this.
Protein secretion systems are involved in nutrient scavenging, motility, adhesion, host cell invasion
and escape, waste release and assembly. The secretion system is used for assembly of membranes,
membrane proteins and the cell wall. Assembly of surface structures:
Adhesins
Invasins
Fibrils
Fimbriae or pili
Conjugative pili
Flagella
Almost 20% of all bacterial proteins are secreted. Membranes are impermeable for proteins, and
proteins are made inside the cytosol. Therefore, a couple of steps are required:
Targeting
o Presence of a signal for secretion
Membrane crossing (twice in Gram-negatives)
o When only one membrane is crossed it is still called secretion
Processing
o Cleavage of the signal for secretion
Correct folding after (and not before) secretion
Gram-negative bacteria need different mechanisms for secretion compared to Gram-positive
bacteria because of the differences in membrane composition. Gram-negative bacteria consist of a
much wider range of secretion systems than Gram-positive bacteria. An efficient and effective
protein secretion requires different secretion mechanisms. Currently there are 7 known secretion
systems.
Common features of secretion systems
Secretion of a protein starts with the ribosome that synthesizes a protein with or without a signal
peptide. Proteins with a signal peptide will eventually be secreted. The secretion system consists of a
protein complex that mediates protein translocation. Assembly of secretion system and secretion of
their substrates (proteins) is usually regulated. Protein secretion is an active process: it consumes
energy (ATP, proton motive force).
1
, Molecular Basis of Bacterial Infections Evelien Floor
Every signal peptide consists of a positively charged N-terminus followed by a hydrophobic site and a
cleavage site. Signal peptidase is responsible for cleavage, if cleavage is absent the protein will
remain in the plasma membrane. Functions of the signal peptide:
Keep the protein unfolded
Targeting to the membrane (translocon)
Insertion hydrophobic (H) domain into the membrane
Secretion across the cytoplasmic membrane
Two main proteins are responsible for secretion across the cytoplasmic membrane: Sec and Tat. Sec
secretes unfolded proteins while Tat secretes folded proteins. Sec is also able to insert membrane
proteins into the inner membrane.
Sec
Sec is the general secretion pathway (GSP) present in all organisms. Most secretory proteins use this
system. Sec also mediates integration of membrane proteins and is involved in assembly of its own
and other secretion complexes.
Sec secretion is possible co-translationally or post-translationally. Co-translational: SRP recognizes
the signal peptide and pushes the protein through the secYEG channel while the ribosome is still
synthesizing the protein. Post-translational secretion can be chaperone-dependent or chaperone-
independent. Post-translational chaperone-dependent: SecA or SecB keep the protein unfolded and
transport the protein to SecYEG. Post-translational chaperone-independent: proteins stay unfolded
in the cytosol without the use of chaperones. Lep is the signal peptidase in E. coli
2
