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New insight into the molecular control of bacterial functional amyloids.

Taylor JD, Matthews SJ - Front Cell Infect Microbiol (2015)

Bottom Line: During this process, aggregation-prone, semi-folded curli subunits have to cross the periplasm and outer-membrane and self-assemble into surface-attached fibers.Two recent breakthroughs have provided molecular details regarding periplasmic chaperoning and subunit secretion.This review offers a combined perspective on these first mechanistic insights into the curli system.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College of Science, Technology and Medicine London, UK.

ABSTRACT
Amyloid protein structure has been discovered in a variety of functional or pathogenic contexts. What distinguishes the former from the latter is that functional amyloid systems possess dedicated molecular control systems that determine the timing, location, and structure of the fibers. Failure to guide this process can result in cytotoxicity, as observed in several pathologies like Alzheimer's and Parkinson's Disease. Many gram-negative bacteria produce an extracellular amyloid fiber known as curli via a multi-component secretion system. During this process, aggregation-prone, semi-folded curli subunits have to cross the periplasm and outer-membrane and self-assemble into surface-attached fibers. Two recent breakthroughs have provided molecular details regarding periplasmic chaperoning and subunit secretion. This review offers a combined perspective on these first mechanistic insights into the curli system.

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Related in: MedlinePlus

The three stages of curli fiber biogenesis. (A) Secretion system assembly: CsgE and CsgG achieve the translocation of CsgF, which folds and binds CsgG. Loss of CsgE results in a dramatic reduction in surface display of CsgF. (B) Pre-secretion subunit handling: Incoming CsgA or CsgB monomers interact with CsgC, which delays spontaneous formation of toxic oligomers. It is expected that subunits within this CsgC-buffered pool (signified by the dashed circle) are either secreted, digested or revert to an amyloidogenic pathway. (C) Subunit secretion, nucleation and fiber assembly: Each curli subunit encounters CsgE (nonamers?) and becomes trapped within the periplasmic cavity of CsgG. Partially folded subunits then traverse the central pore and are released into the extracellular milieu. The folding pathway of periplasmic CsgA determines the appearance and properties of extracellular fibers, thus it is unlikely that CsgA is secreted as a linear polypeptide. Once outside the cell, CsgB is interacts with CsgF and initiates nucleation of the CsgA fiber.
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Figure 2: The three stages of curli fiber biogenesis. (A) Secretion system assembly: CsgE and CsgG achieve the translocation of CsgF, which folds and binds CsgG. Loss of CsgE results in a dramatic reduction in surface display of CsgF. (B) Pre-secretion subunit handling: Incoming CsgA or CsgB monomers interact with CsgC, which delays spontaneous formation of toxic oligomers. It is expected that subunits within this CsgC-buffered pool (signified by the dashed circle) are either secreted, digested or revert to an amyloidogenic pathway. (C) Subunit secretion, nucleation and fiber assembly: Each curli subunit encounters CsgE (nonamers?) and becomes trapped within the periplasmic cavity of CsgG. Partially folded subunits then traverse the central pore and are released into the extracellular milieu. The folding pathway of periplasmic CsgA determines the appearance and properties of extracellular fibers, thus it is unlikely that CsgA is secreted as a linear polypeptide. Once outside the cell, CsgB is interacts with CsgF and initiates nucleation of the CsgA fiber.

Mentions: CsgG occurs in the outer-membrane as a novel nonameric, 36-stranded beta-barrel, with a central pore allowing passage for outgoing curli subunits (Figure 2). A remarkable feature of this protein is the large cavity (5 nm) within the β-barrel, which in other large membrane proteins is typically filled by a plug domain (e.g., FhuA, Ferguson et al., 1998 and PapC, Remaut et al., 2008). The wall of this cavity is lined with conserved polar or negatively-charged side-chains, which are thought to be important for proper export of curli subunits (Cao et al., 2014). CsgF is surface-localized and anchors CsgB at the base of nascent fibers (Nenninger et al., 2009). It is assumed that CsgG is responsible for secretion of CsgF however this has not been directly proven. Given the unusual absence of large extracellular loops within CsgG, it seems conceivable that CsgF inserts into this cavity and presents a binding site for CsgB (Figure 2). Although Cao et al. tested point mutants to probe the importance of this region, only a triple mutant showed a significant defect in curli formation (Cao et al., 2014).


New insight into the molecular control of bacterial functional amyloids.

Taylor JD, Matthews SJ - Front Cell Infect Microbiol (2015)

The three stages of curli fiber biogenesis. (A) Secretion system assembly: CsgE and CsgG achieve the translocation of CsgF, which folds and binds CsgG. Loss of CsgE results in a dramatic reduction in surface display of CsgF. (B) Pre-secretion subunit handling: Incoming CsgA or CsgB monomers interact with CsgC, which delays spontaneous formation of toxic oligomers. It is expected that subunits within this CsgC-buffered pool (signified by the dashed circle) are either secreted, digested or revert to an amyloidogenic pathway. (C) Subunit secretion, nucleation and fiber assembly: Each curli subunit encounters CsgE (nonamers?) and becomes trapped within the periplasmic cavity of CsgG. Partially folded subunits then traverse the central pore and are released into the extracellular milieu. The folding pathway of periplasmic CsgA determines the appearance and properties of extracellular fibers, thus it is unlikely that CsgA is secreted as a linear polypeptide. Once outside the cell, CsgB is interacts with CsgF and initiates nucleation of the CsgA fiber.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389571&req=5

Figure 2: The three stages of curli fiber biogenesis. (A) Secretion system assembly: CsgE and CsgG achieve the translocation of CsgF, which folds and binds CsgG. Loss of CsgE results in a dramatic reduction in surface display of CsgF. (B) Pre-secretion subunit handling: Incoming CsgA or CsgB monomers interact with CsgC, which delays spontaneous formation of toxic oligomers. It is expected that subunits within this CsgC-buffered pool (signified by the dashed circle) are either secreted, digested or revert to an amyloidogenic pathway. (C) Subunit secretion, nucleation and fiber assembly: Each curli subunit encounters CsgE (nonamers?) and becomes trapped within the periplasmic cavity of CsgG. Partially folded subunits then traverse the central pore and are released into the extracellular milieu. The folding pathway of periplasmic CsgA determines the appearance and properties of extracellular fibers, thus it is unlikely that CsgA is secreted as a linear polypeptide. Once outside the cell, CsgB is interacts with CsgF and initiates nucleation of the CsgA fiber.
Mentions: CsgG occurs in the outer-membrane as a novel nonameric, 36-stranded beta-barrel, with a central pore allowing passage for outgoing curli subunits (Figure 2). A remarkable feature of this protein is the large cavity (5 nm) within the β-barrel, which in other large membrane proteins is typically filled by a plug domain (e.g., FhuA, Ferguson et al., 1998 and PapC, Remaut et al., 2008). The wall of this cavity is lined with conserved polar or negatively-charged side-chains, which are thought to be important for proper export of curli subunits (Cao et al., 2014). CsgF is surface-localized and anchors CsgB at the base of nascent fibers (Nenninger et al., 2009). It is assumed that CsgG is responsible for secretion of CsgF however this has not been directly proven. Given the unusual absence of large extracellular loops within CsgG, it seems conceivable that CsgF inserts into this cavity and presents a binding site for CsgB (Figure 2). Although Cao et al. tested point mutants to probe the importance of this region, only a triple mutant showed a significant defect in curli formation (Cao et al., 2014).

Bottom Line: During this process, aggregation-prone, semi-folded curli subunits have to cross the periplasm and outer-membrane and self-assemble into surface-attached fibers.Two recent breakthroughs have provided molecular details regarding periplasmic chaperoning and subunit secretion.This review offers a combined perspective on these first mechanistic insights into the curli system.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College of Science, Technology and Medicine London, UK.

ABSTRACT
Amyloid protein structure has been discovered in a variety of functional or pathogenic contexts. What distinguishes the former from the latter is that functional amyloid systems possess dedicated molecular control systems that determine the timing, location, and structure of the fibers. Failure to guide this process can result in cytotoxicity, as observed in several pathologies like Alzheimer's and Parkinson's Disease. Many gram-negative bacteria produce an extracellular amyloid fiber known as curli via a multi-component secretion system. During this process, aggregation-prone, semi-folded curli subunits have to cross the periplasm and outer-membrane and self-assemble into surface-attached fibers. Two recent breakthroughs have provided molecular details regarding periplasmic chaperoning and subunit secretion. This review offers a combined perspective on these first mechanistic insights into the curli system.

Show MeSH
Related in: MedlinePlus