User:Ed0578/Curli

Curli fibers, and thus the curli protein, are coded by two operons, the csgBAC and csgDEFG operon.
Curli fibers, and thus the curli protein, are coded by two operons, the csgBAC and csgDEFG operon, in total containing seven genes. The csgBAC operon is responsible for the coding the three proteins CsgB, CsgA, and CsgC, all responsible for either the major subunit formation within the curli fiberal, or the inhibition of it. The csgDEFG operon codes for proteins CsgD, CsgE, CsgF, and CsgG, responsible for the assembly, translocation, and regulation of the curli protein.

Function
Amyloids have been linked to illnesses such as Alzheimer's, Parkinson's, Huntington's, lupus, among many more. Additionally, the Curli protein is considered a PAMP (Pathogen-associated molecular pattern) and so Curli's beta sheet structure acts on the innate immune system, activating the TLR2 (Toll-Like Receptor 2). This then causes a downstream response by a producing proinflammatory response where proinflammatory cytokines and chemokines are recruited to initiation and inflammation response.

Curli, however, has other functions (thus being coined a "functional amyloid" ) including being a major component in the biofilm generated by gram-negative bacterial such as E. coli and Salmonella. These biofilms allow gram-negative bacteria to better colonize in a given environment, protecting them from oxidative stress and dehydration. These biofilms, however, call for much concern. As these biofilms allow for the bacteria to survive chemical and physical stressors within their environment, not only does it make patients more susceptible to infection when using shared appliances, but Curli and other biofilms have shown to reduce the infected individuals immune response and antimicrobials. Curli proteins and biofilms alike are very resistant to chemical stressors to a point where stronger pretreatment is required in order for Curli to degrade or dissolve in sodium dodecyl sulphate (SDS).

Structure
The curli protein's main components consist (subunits) of the CsgA and CsgB protein.

CsgA
CsgA is the major subunit of the Curli protein at 13.1 kiloDalton. This protein consists of three domains which have a tendency to aggregate to form amyloid fibrils, a single peptide, a 22 amino acid N terminal sequence (used for secretion) and an amyloid core domain at the C-terminal sequence. Furthermore, the amyloid core domain is composed of 5 repeating (yet not exact) sequences revolving around the sequence: Ser-X5-Gln-X-Gly-X-Gly-Asn-X-Ala-X3-Gln. This repeating sequence is the characteristic subunit that forms the aggregatable β-sheet.

CsgB
CsgB, also known as the minor subunit, is required for the nucleation and organization of CsgA into a Curli fiber on the cells surface. CsgB has a very similar repeating sequence to that of CsgA with the expectation that one of the 5 repeating sequences does contains additional amino acids, known as Lys133, Arg140, Arg14, and Arg151. This change in the final subunit (known as the R5 subunit) is required. Without the presence of the R5 subunit, or the changes within the subunit, CsgA can not properly form on the cell surface.

CsgC
The CsgC subunit only recently was discovered to prevent the aggregation and polymerization of the CsgA protein. Without it, there is a chance for amyloid fibril formation and eventual cell death. Multiple experiments isolating CsgC away from the CsgA and CsgB subunit caused for CsgA to aggregate into fibrils, and therefore possibly leading to the downstream effects on illnesses such as Alzheimer's. The molar ratio required for CsgC to inhibit CsgA is 1:500, thus meaning only 1 CsgC protein is required to inhibit 500 CsgA proteins from forming amyloid fibril structures. It is hypothesized that CsgC is therefore considered a chaperone as it prevents further CsgA nucleation, rather allowing CsgA to form into its proper structure instead of aggregating.