Part:BBa_K4990003
mFadA A-domain
What you need to know!
Many bacteria have long chain fiber-protein complexes on their surfaces, which are called pili or fimbriae. These pili are composed of individual pilus monomers that link together head-to-tail in the extracellular environment, self-assembling into long chain fibers with high physical strength.
For Fusobacterium nucleatum, its pili are referred to as FadA (Fusobacterium adhesin A). The monomers that make up these pili come in two forms: ①pre-FadA, which serves as an anchoring structure, attaching the entire pilus to the bacterial inner membrane. ②mature Fusobacterium adhesin A (mFadA), which can link head-to-tail and self-assemble into a long filament.
Fusobacterium nucleatum (Fn) is a Gram-negative bacterium that exists in the human body permanantly, tending to accumulate in the tumor sites of colorectal cancer. The bacterial fimbrial protein, FadA, located on its surface, can bind with E-cadherin on the surface of colorectal cancer cells. This binding facilitates the adhesion and invasion of Fusobacterium nucleatum, activating the Wnt/β-catenin signaling pathway, resulting in the overexpression of oncogenes and promoting the growth of colorectal cancer cells.
However, displaying the entire bacterial pilus monomer directly on the surface would lead to a range of issues, including steric hindrance, nonspecificity, and metabolic waste. Therefore, we truncated the mFadA to address these concerns.
What it is?
Below is the structure of the mFadA B-domain, which is truncated from the pili monomer of Fn:
It functions like bait, enticing the Fusobacterium nucleatum to take the hook.
What can it do?
However, not the entire structure of mFadA is involved in self-assembly. Thus, we considered removing unnecessary domains. Upon closer examination of mFadA's structure, we divided it into two domains: Domain A and Domain B. Domain A comprises two anti-parallel α-helical structures, while Domain B consists of a single anti-parallel α-helix. We believe that Domain B is the most crucial. On a microscale, it possesses the function of binding with Domain A, and on a macroscale, it exhibits the capability to target Fn (Fusobacterium nucleatum).
Therefore, by displaying the engineered bacteria with the mFadA B-domain on their surface, specific adhesion to Fn can be achieved, enabling bacteria-bacteria targeting.
Sequence and Features
- 10INCOMPATIBLE WITH RFC[10]Illegal PstI site found at 97
- 12INCOMPATIBLE WITH RFC[12]Illegal PstI site found at 97
- 21COMPATIBLE WITH RFC[21]
- 23INCOMPATIBLE WITH RFC[23]Illegal PstI site found at 97
- 25INCOMPATIBLE WITH RFC[25]Illegal PstI site found at 97
- 1000COMPATIBLE WITH RFC[1000]
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