The Type V secretion system was first described twenty years ago. Since then, much work has be done to elucidate functional aspects of members of this family and their mechanisms of biogenesis. What was once considered to be a quirky one-off system, with the discovery of the IgA1 protease secretion system of Neisseria gonorrhoeae, has been revealed as the largest family of secreted proteins amongst the Gram-negative bacteria.

The type V secretion system (T5SS) is comparatively is less complex than types I to IV. This secretion mechanism has been subdivided into sub-types (a), (b) and (c), as variations upon a theme were discovered. Each polypeptide secreted via the T5SS contains an N-terminal Sec-dependant signal sequence required to direct inner membrane export. The significant functional domain classifying molecules into these secretion systems is the dedicated outer membrane (outer membrane) β-barrel protein domain, through which secretion of the effector molecule is achieved.

from Scott-Tucker and Henderson in Bacterial Secreted Proteins

Further reading:

1. Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis
2. Microbiology Books

Labels: bacteria, protein, protein secretion, proteins

Type IV secretion systems are multiprotein complexes that mediate the translocation of macromolecules (proteins, DNA or DNA-protein complexes) across the bacterial cell envelope into the extracellular medium or directly into recipient cells. This strategy is exploited for the delivery of effector molecules that modulate host cell interactions by bacterial pathogens and symbionts. Type IV secretion systems also mediate the translocation of DNA molecules from bacteria and the uptake of DNA into bacteria and thereby contribute to horizontal gene transfer.

The term type IV secretion system (T4SS) was originally based on the significant sequence similarities between the protein components of macromolecular transporters used for plasmid transfer and for the delivery of virulence factors from bacterial pathogens to their hosts. The two first examples that prompted the proposal of T4SSs as a distinct family of macromolecular transporters were the conjugative plasmid RP4 transfer machinery (Trb) and the VirB/D4 machinery used by the plant pathogen Agrobacterium tumefaciens for the delivery of single-stranded DNA and of protein virulence factors to plants.

T4SSs carry out one of three functions. The first group of T4SSs translocates exclusively DNA and serves for the uptake or secretion of genetic information. The second group translocates DNA molecules as well as proteins from donor to recipient cells. The third group exclusively translocates proteins and those are either secreted into the exterior medium or directly into recipient cells.

Since the original proposal that T4SS constitute a distinct class of secretion systems was made, the number of known T4SS has continued to grow and both metagenomic as well as functional analyses continue to add new examples. Since many T4SSs localize on plasmids they can be transmitted by horizontal gene transfer and this has very interesting implications for their evolution.

from Christian Baron in Bacterial Secreted Proteins

Further reading:

1. Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis
2. Microbiology Books

Labels: bacteria, protein, protein secretion, proteins

The type-III secretion system (T3SS) is an export machine used by pathogenic Gram-negative bacteria to deliver proteins straight into the eukaryotic cytosol with the aim to subvert the host cell defense. After the discovery of T3S in 1990, significant progress has been made in the understanding of its structure, assembly and function. The basic structure consisting of the membrane-embedded basal body, the needle and the tip structure has been analyzed in more detail. The composition of several structural components has been determined and important insights into the assembly process have been gained. The relationship between the T3SS of pathogenic bacteria and the flagellum has been noted. Besides the structural similarities, the assembly of these two nanomachines shows some commonalities, for example the length control of external structures such as the T3 needle and the flagellar hook. The T3SS also includes the pore forming translocator proteins, effector proteins and a set of specific chaperones. A recent review on the type-III secretion system focuses on the structure and assembly of this fascinating nanomachine.

from Sorg and Cornelis in Bacterial Secreted Proteins

Further reading:

1. Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis
2. Microbiology Books

Labels: bacteria, protein, protein secretion, proteins

Gram-negative bacteria have evolved several secretory pathways to release proteins or toxic factors into their surrounding environment. Many virulence determinants, including extracellular toxins and proteases, are secreted by the type II secretion system (T2SS) which is widely conserved and common among γ-proteobacteria.

Typical T2SSs are composed of 12 to 16 proteins termed Gsp (General secretion pathway) proteins. These components associate in a multiprotein complex that constitutes a large structure (the secreton) that spans the periplasm and is thought to connect inner and outer membranes. Exoproteins that use the T2SS are characterized by the presence of a leader peptide (or signal peptide) at their N terminus and are secreted in the extracellular medium by a two-step process involving a transient periplasmic intermediate. The T2SS is unique in its ability to promote secretion of large multimeric proteins that are folded in the periplasm. The system is also characterized by a species-specificity, which is mainly related to the GspC and GspD components, the gatekeepers.

Although relatively little attention has been payed to the regulation of T2SSs, it was observed that expression of most of the genes encoding T2SS-dependent exoproteins is growth phase-dependent or strictly regulated by environmental signals. In Pseudomonas aeruginosa, T2SS assembly and most of the T2SS-dependent exoproteins are regulated via quorum sensing, a mechanism that senses the density of a surrounding bacterial population.

Besides typical T2SSs, some secretory systems are found which contain all the T2SS components but in a different genetic organization. Some incomplete systems have also been described which contain genes homologous to T2SS but dispersed on the bacterial chromosome. Components of these systems can either associate with classical T2SS components to constitute a functional hybrid machinery or represent peculiar systems with strictly defined functions.

from Michel and Voulhoux in Bacterial Secreted Proteins

Further reading:

1. Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis
2. Pseudomonas: Genomics and Molecular Biology
3. Microbial Toxins: Current Research and Future Trends

Labels: bacteria, protein, protein secretion, proteins, Pseudomonas, toxin

Bacteria have developed numerous systems to secrete proteins or DNA in order to modify their immediate surroundings or to obtain an advantage in a competitive and hostile environment. Since Gram-negative bacteria possess two membranes, the inner (cytoplasmic) membrane and the outer membrane, transport machines for protein secretion have the challenging task of circumventing two barriers to reach the exterior. A rather simple transport apparatus, the Type I secretion machinery, composed of only three proteins residing in the inner and outer membrane of Gram-negative bacteria achieve this objective in a single step. The Type I secretion pathway although also present in Gram-positive bacteria, has been analysed in greatest detail in Gram-negative bacteria. Almost all Type I transport substrates are polypeptides, varying from the small Escherichia coli peptide colicin V, (10 kDa) to the large Pseudomonas fluorescens cell adhesion protein LapA of 900 kDa. While these two examples reflect the range of the size of Type I transport substrates, the best characterized are the RTX toxins and the lipases. Type I secretion is also involved in export of non-proteinaceous substrates like cyclic β-glucans or polysaccharides.

from Jenewein et al in Bacterial Secreted Proteins

Further reading:

1. Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis
2. Pseudomonas: Genomics and Molecular Biology
3. Microbial Toxins: Current Research and Future Trends

Labels: bacteria, protein, protein secretion, proteins, Pseudomonas, toxin

A description of the twin-arginine translocation (Tat) pathway continues our series on protein secretion in microorganisms.

The twin-arginine translocation (Tat) pathway is a protein transport system in bacteria, archaea and chloroplasts with the ability to export proteins in a fully folded conformation. Proteins are targeted to the Tat pathway by an N-terminal signal peptide containing an almost invariant twin-arginine sequence motif. Pretranslocational folding is necessitated by the incorporation of metallo-cofactors, assembly into oligomeric complexes, and presumably rapid folding kinetics. Many Tat systems comprise three functionally individual membrane proteins, termed TatA, TatB, and TatC, whereas especially Gram-positive bacteria possess minimal TatAC translocases, in which TatA functionally replaces TatB. TatC and TatB form a complex that is involved in recognition of Tat signal sequences and their insertion into the membrane. TatA mediates the actual translocation event, but it is unclear whether it does so by forming the pore-like structures that it displays when purified to homogeneity. Energy is derived from either component of the proton-motive force, ΔpH or ΔΨ, and is required only for late steps following signal sequence cleavage. Substrates that either lack the twin-arginine pair or are in a malfolded conformation in general are not translocated. The mechanisms by which non-functional substrates are rejected are not understood. For cofactor-containing substrates, proof-reading seems to depend on the activity of specific cytosolic chaperones.

from Panahandeh et al in Bacterial Secreted Proteins

Further reading: Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis

Labels: archaea, bacteria, protein, protein secretion, proteins

Protein secretion is an important process for bacteria and is particularly important to bacterial pathogens. Secreted proteins have a range of biological functions.

The majority of proteins destined for export across the microbial cytoplasmic membrane or integration into the membrane are handled by the evolutionarily conserved Sec system. The Sec substrates have specific topogenic signals and are targeted to the membrane-embedded SecYEG translocon that serves as a polypeptide-conducting channel either co-translationally by SRP for lipid-phase integration or post-translationally by SecB for complete translocation. The plug helix of SecY that clogs the unused channel and the central constriction that seals around the translocating chain make the translocon function compatible with the permeability barrier of the membrane. The translocon also contains a lateral gate, through which it not only accepts a newly synthesized client protein but also allows its hydrophobic segment, if any, to partition into the lipid phase. The post-translational mode of translocation, characteristic of the bacterial systems, is driven by the SecA ATPase, which interacts with SecY and a preprotein and accordingly undergoes conformational transitions coupled with the ATPase cycles.

from Ito and Mori in Bacterial Secreted Proteins

Further reading: Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis

Labels: pathogen, pathogenic, protein, protein secretion, proteins