Flagellin

Image:EMpylori.jpg electron micrograph, showing multiple flagella on the cell surface]]

The structure of flagellin is responsible for the helical shape of the flagellar filament, which is important for its proper function.{{cite journal | vauthors = Steiner TS | title = How flagellin and toll-like receptor 5 contribute to enteric infection | journal = Infection and Immunity | volume = 75 | issue = 2 | pages = 545–52 | date = February 2007 | pmid = 17118981 | pmc = 1828527 | doi = 10.1128/IAI.01506-06 }} It is transported through the center of the filament to the tip where it polymerases spontaneously into a part of the filament. In E. coli it is unfolded by the flagellar secretion chaperone FliS ({{UniProt|P26608}}) during transport.{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK6250 |title=Structure, Function and Assembly of Flagellar Axial Proteins | vauthors = Vonderviszt F, Keiichi N |publisher=Madame Curie Bioscience Database |location=Austin, TX|year=2013 }} The filament is made up of eleven smaller "protofilaments", nine of which contains flagellin in the L-type shape and the other two in the R-type shape.{{cite journal | vauthors = Maki-Yonekura S, Yonekura K, Namba K | title = Conformational change of flagellin for polymorphic supercoiling of the flagellar filament | journal = Nature Structural & Molecular Biology | volume = 17 | issue = 4 | pages = 417–22 | date = April 2010 | pmid = 20228803 | doi = 10.1038/nsmb.1774 | s2cid = 31915502 }}

The helical N- and C-termini of flagellin form the inner core of the flagellin protein, and is responsible for flagellin's ability to polymerize into a filament. The middle residues make up the outer surface of the flagellar filament. While the termini of the protein are quite similar among all bacterial flagellins, the middle portion is wildly variable and can be absent in some species. The flagellin domains are numbered from the helical core (D0/D1) to the outside (D2, ...); when viewed from the amino-acid sequence, D0/D1 appears on the two termini. Flagellin-like structural proteins are found in other portions of the flagellum, such as the hook (flgE; {{UniProt|P75937}}), the rod at the base, and the cap at the top.{{cite journal | vauthors = Imada K | title = Bacterial flagellar axial structure and its construction | journal = Biophysical Reviews | volume = 10 | issue = 2 | pages = 559–570 | date = April 2018 | pmid = 29235079 | pmc = 5899737 | doi = 10.1007/s12551-017-0378-z }}

The middle part of  E. coli (and related) flagellin, D3, displays a beta-folium fold and appears to maintain flagellar stability.{{cite journal | vauthors = Samatey FA, Imada K, Nagashima S, Vonderviszt F, Kumasaka T, Yamamoto M, Namba K | title = Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling | journal = Nature | volume = 410 | issue = 6826 | pages = 331–7 | date = March 2001 | pmid = 11268201 | doi = 10.1038/35066504 | bibcode = 2001Natur.410..331S | s2cid = 4416455 }}

Mammals often have acquired immune responses (T-cell and antibody responses){{cite journal | vauthors = Genta RM | title = The immunobiology of Helicobacter pylori gastritis | journal = Seminars in Gastrointestinal Disease | volume = 8 | issue = 1 | pages = 2–11 | date = January 1997 | pmid = 9000497 }} to flagellated bacterium, which occur frequently to flagellar antigens. Flagellin has also been shown to directly interact with TLR5 on T cells{{cite journal | vauthors = Sharma N, Akhade AS, Qadri A | title = Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells | journal = Journal of Leukocyte Biology | volume = 93 | issue = 4 | pages = 521–8 | date = April 2013 | pmid = 23345392 | doi = 10.1189/jlb.0712328 | doi-access = | s2cid = 21897008 }} and TLR11.{{cite journal | vauthors = Hatai H, Lepelley A, Zeng W, Hayden MS, Ghosh S | title = Toll-Like Receptor 11 (TLR11) Interacts with Flagellin and Profilin through Disparate Mechanisms | journal = PLOS ONE | volume = 11 | issue = 2 | pages = e0148987 | date = 2016 | pmid = 26859749 | pmc = 4747465 | doi = 10.1371/journal.pone.0148987 | bibcode = 2016PLoSO..1148987H | doi-access = free }} Some bacteria are able to switch between multiple flagellin genes in order to evade this response.

Flagellins contain a Toll-like receptor 5 (TLR5) epitope, a region recognized by the immune receptor TLR5. There are variations in the strength of flagellin binding and its ability to activate TLR5. Flagellins can be classified into three groups based on these characteristics: silent flagellins, evaders and stimulators. Silent flagellins bind to TLR5 but do not induce signaling. Evaders are incapable of binding and, consequently, do not trigger TLR5 activation. Stimulators exhibit variable binding capabilities to TLR5 yet possess the ability to activate TLR5.DOI: 10.1126/sciimmunol.abq7001

The propensity of the immune response to flagellin may be explained by two facts:

• Flagellin is an extremely abundant protein in flagellated bacteria.
• There exists a specific innate immune receptor that recognizes flagellin, Toll-like receptor 5 (TLR5).{{cite journal | vauthors = Kathrani A, Holder A, Catchpole B, Alvarez L, Simpson K, Werling D, Allenspach K | title = TLR5 risk-associated haplotype for canine inflammatory bowel disease confers hyper-responsiveness to flagellin | journal = PLOS ONE | volume = 7 | issue = 1 | pages = e30117 | date = 2012 | pmid = 22279566 | pmc = 3261174 | doi = 10.1371/journal.pone.0030117 | bibcode = 2012PLoSO...730117K | doi-access = free }}

In addition, a 22-amino acid sequence (flg22) of the conserved N-terminal part of flagellin is known to activate plant defense mechanisms.{{cite journal | vauthors = García AV, Hirt H | title = Salmonella enterica induces and subverts the plant immune system | journal = Frontiers in Microbiology | volume = 5 | pages = 141 | date = 2014-01-01 | pmid = 24772109 | pmc = 3983520 | doi = 10.3389/fmicb.2014.00141 | doi-access = free }} Flagellin perception in Arabidopsis thaliana functions via the receptor-like-kinase FLS2 (FLAGELLIN SENSING 2).{{cite journal | vauthors = Gómez-Gómez L, Boller T | title = FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis | journal = Molecular Cell | volume = 5 | issue = 6 | pages = 1003–11 | date = June 2000 | pmid = 10911994 | doi = 10.1016/S1097-2765(00)80265-8 | doi-access = free }} Upon flg22 detection, FLS2 quickly binds to BAK1 (BRI1-associated kinase 1) to initiate signaling by reciprocal transphosphorylation of their kinase domains.{{cite journal | vauthors = Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nürnberger T, Jones JD, Felix G, Boller T | title = A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence | journal = Nature | volume = 448 | issue = 7152 | pages = 497–500 | date = July 2007 | pmid = 17625569 | doi = 10.1038/nature05999 | bibcode = 2007Natur.448..497C | url = http://edoc.mpg.de/318857 | hdl = 11858/00-001M-0000-0012-3840-F | s2cid = 2818791 | hdl-access = free }} Both flagellin and UV-C act similarly to increase homologous recombination, as demonstrated by Molinier et al 2006. Beyond this somatic effect, they found this to extend to subsequent generations of the plant.{{cite journal | last1=Urban | first1=L. | last2=Chabane Sari | first2=D. | last3=Orsal | first3=B. | last4=Lopes | first4=M. | last5=Miranda | first5=R. | last6=Aarrouf | first6=J. | title=UV-C light and pulsed light as alternatives to chemical and biological elicitors for stimulating plant natural defenses against fungal diseases | journal=Scientia Horticulturae | publisher=Elsevier | volume=235 | year=2018 | issn=0304-4238 | doi=10.1016/j.scienta.2018.02.057 | pages=452–459 | s2cid=90436989}} Mitogen-activated-protein-kinases (MAPK) acts as downstream signaling compounds, leading ultimately to PAMP-triggered immunity in which more than 900 genes are up-/down-regulated upon flg22 treatment.{{citation needed|date=October 2021}}

Pre-stimulation with a synthetic flg22-peptide led to enhanced resistance against bacterial invaders.{{Cite journal |last1=Zipfel |first1=Cyril |last2=Robatzek |first2=Silke |last3=Navarro |first3=Lionel |last4=Oakeley |first4=Edward J. |last5=Jones |first5=Jonathan D. G. |last6=Felix |first6=Georg |last7=Boller |first7=Thomas |date=April 2004 |title=Bacterial disease resistance in Arabidopsis through flagellin perception |url=http://www.nature.com/articles/nature02485 |journal=Nature |language=en |volume=428 |issue=6984 |pages=764–767 |doi=10.1038/nature02485 |pmid=15085136 |bibcode=2004Natur.428..764Z |s2cid=4332562 |issn=0028-0836|url-access=subscription }}

{{reflist}}

• {{MeshName|Flagellin}}
• Bacterial flagellin and plant disease resistance, published by Zipfel. et al. (2004) [http://www.nature.com/nature/journal/v428/n6984/abs/nature02485.html) Abstract Article]

Category:Bacterial proteins