Flagellin

Last updated
Flagellin
Identifiers
SymbolFlagellin
Pfam PF00700
InterPro IPR001492
SCOP2 1ucu / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Flagellins are a family of proteins present in flagellated bacteria [1] which arrange themselves in a hollow cylinder to form the filament in a bacterial flagellum. Flagellin has a mass on average of about 40,000 daltons. [2] [3] Flagellins are the principal component of bacterial flagella that have a crucial role in bacterial motility.

Contents

The gene that encodes for flagellin has a different name in different bacterial species such as flaA ( Helicobacter pylori for example), fliC, fljB. [4] [1]

Structure

Helicobacter pylori electron micrograph, showing multiple flagella on the cell surface EMpylori.jpg
Helicobacter pylori 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. [4] 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 ( P26608 ) during transport. [5] 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. [6]

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; P75937 ), the rod at the base, and the cap at the top. [7]

The middle part of  E. coli (and related) flagellin, D3, displays a beta-folium fold and appears to maintain flagellar stability. [8]

Immune response

In mammals

Mammals often have acquired immune responses (T-cell and antibody responses) [9] to flagellated bacterium, which occur frequently to flagellar antigens. Flagellin has also been shown to directly interact with TLR5 on T cells [10] and TLR11. [11] 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. [12]

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

In plants

In addition, a 22-amino acid sequence (flg22) of the conserved N-terminal part of flagellin is known to activate plant defence mechanisms. [14] Flagellin perception in Arabidopsis thaliana functions via the receptor-like-kinase FLS2 (FLAGELLIN SENSING 2). [15] Upon flg22 detection, FLS2 quickly binds to BAK1 (BRI1-associated kinase 1) to initiate signalling by reciprocal transphosphorylation of their kinase domains. [16] 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. [17] Mitogen-activated-protein-kinases (MAPK) acts as downstream signalling compounds, leading ultimately to PAMP-triggered immunity in which more than 900 genes are up-/down-regulated upon flg22 treatment.[ citation needed ]

Pre-stimulation with a synthetic flg22-peptide led to enhanced resistance against bacterial invaders. [18]

Related Research Articles

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<i>Arabidopsis thaliana</i> Model plant species in the family Brassicaceae

Arabidopsis thaliana, the thale cress, mouse-ear cress or arabidopsis, is a small plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally considered a weed.

<span class="mw-page-title-main">Flagellum</span> Cellular appendage functioning as locomotive or sensory organelle

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<span class="mw-page-title-main">Toll-like receptor</span> Class of immune system proteins

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.

Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus, protect the host from infection.

Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, as well as by epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.

<span class="mw-page-title-main">Innate immune system</span> Immunity strategy in living beings

The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.

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<span class="mw-page-title-main">IRAK4</span> Protein-coding gene in humans

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The gene-for-gene relationship is a concept in plant pathology that plants and their diseases each have single genes that interact with each other during an infection. It was proposed by Harold Henry Flor who was working with rust (Melampsora lini) of flax (Linum usitatissimum). Flor showed that the inheritance of both resistance in the host and parasite ability to cause disease is controlled by pairs of matching genes. One is a plant gene called the resistance (R) gene. The other is a parasite gene called the avirulence (Avr) gene. Plants producing a specific R gene product are resistant towards a pathogen that produces the corresponding Avr gene product. Gene-for-gene relationships are a widespread and very important aspect of plant disease resistance. Another example can be seen with Lactuca serriola versus Bremia lactucae.

<span class="mw-page-title-main">Integrin-linked kinase</span> Protein-coding gene in the species Homo sapiens

Integrin-linked kinase is an enzyme that in humans is encoded by the ILK gene involved with integrin-mediated signal transduction. Mutations in ILK are associated with cardiomyopathies. It is a 59kDa protein originally identified in a yeast-two hybrid screen with integrin β1 as the bait protein. Since its discovery, ILK has been associated with multiple cellular functions including cell migration, proliferation, and adhesion.

<span class="mw-page-title-main">Toll-like receptor 5</span> Protein found in humans

Toll-like receptor 5, also known as TLR5, is a protein which in humans is encoded by the TLR5 gene. It is a member of the toll-like receptor (TLR) family. TLR5 is known to recognize bacterial flagellin from invading mobile bacteria. It has been shown to be involved in the onset of many diseases, including Inflammatory bowel disease due to the high expression of TLR in intestinal lamina propria dendritic cells. Recent studies have also shown that malfunctioning of TLR5 is likely related to rheumatoid arthritis, osteoclastogenesis, and bone loss. Abnormal TLR5 functioning is related to the onset of gastric, cervical, endometrial and ovarian cancers.

Resistance genes (R-Genes) are genes in plant genomes that convey plant disease resistance against pathogens by producing R proteins. The main class of R-genes consist of a nucleotide binding domain (NB) and a leucine rich repeat (LRR) domain(s) and are often referred to as (NB-LRR) R-genes or NLRs. Generally, the NB domain binds either ATP/ADP or GTP/GDP. The LRR domain is often involved in protein-protein interactions as well as ligand binding. NB-LRR R-genes can be further subdivided into toll interleukin 1 receptor (TIR-NB-LRR) and coiled-coil (CC-NB-LRR).

BRI1-associated receptor kinase 1 is an important plant protein that has diverse functions in plant development.

Mitogen-activated protein kinase (MAPK) networks are the pathways and signaling of MAPK, which is a protein kinase that consists of amino acids serine and threonine. MAPK pathways have both a positive and negative regulation in plants. A positive regulation of MAPK networks is to help in assisting with stresses from the environment. A negative regulation of MAPK networks is pertaining to a high quantity of reactive oxygen species (ROS) in the plant.

<span class="mw-page-title-main">Leucine-rich repeat receptor like protein kinase</span>

Leucine-rich repeat receptor like protein kinase are plant cell membrane localized Leucine-rich repeat (LRR) receptor kinase that play critical roles in plant innate immunity. Plants have evolved intricate immunity mechanism to combat against pathogen infection by recognizing Pathogen Associated Molecular Patterns (PAMP) and endogenous Damage Associated Molecular Patterns (DAMP). PEPR 1 considered as the first known DAMP receptor of Arabidopsis.

<span class="mw-page-title-main">EF-Tu receptor</span> Pattern-recognition receptor (PRR)

EF-Tu receptor, abbreviated as EFR, is a pattern-recognition receptor (PRR) that binds to the prokaryotic protein EF-Tu in Arabidopsis thaliana. This receptor is an important part of the plant immune system as it allows the plant cells to recognize and bind to EF-Tu, preventing genetic transformation by and protein synthesis in pathogens such as Agrobacterium.

<span class="mw-page-title-main">High Affinity K+ transporter HAK5</span>

High Affinity K+ transporter HAK5 is a transport protein found on the cell surface membrane of plants under conditions of potassium deprivation. It is believed to act as a symporter for protons and the potassium ion, K+. Firstly discovered in barley, receiving the name of HvHAK1, it was soon after identified in the model plant Arabidopsis thaliana and named HAK5. These transporters belongs to the subgroup I of the KT-HAK-KUP family of plant proteins with obvious homology with both bacterial and fungal transport systems, which experienced a major diversification following land conquest. KT-HAK-KUP transporters are one of four different types of K+ transporter within the cell, but are unique as they do not have a putative pore forming domain like the other three; Shaker channels, KCO channels, HKT transporters. It is activated when the plant is situated in low soil with low potassium concentration, and has been shown to be located in higher concentration in the epidermis and vasculature of K+ deprived plants. By turning on, it increases the plants affinity (uptake) of potassium. Potassium plays a vital role in the plants growth, reproduction, immunity, ion homeostasis, and osmosis, which ensures the plants survival. It is the highest cationic molecule within the plant, accounting for 10% of the plants dry weight, which makes its uptake into the plant important. Each plant species has its own HAK5 transporter that is specific to that species and has different levels of affinity to K+. To operate and activate the HAK5 transporter, the external concentration of K+ must be lower than 10μM and up to 200μM. In Arabidopsis plants, when external potassium concentration is lower than 10μM, it is only HAK5 that is involved with the uptake of K+, then between 10 and 200μM both HAK5 and AKT1 are involved with the uptake of K+. HAK5 is coupled with CBL9/CIPK23 kinase's although the mechanism behind this has not yet been understood.

<span class="mw-page-title-main">FLS2</span>

FLS genes have been discovered to be involved in flagellin reception of bacteria. FLS1 was the original gene discovered shown to correspond with a specific ecotype within Arabidopsis thaliana. Even so, further studies have shown a second FLS gene known as FLS2 that is also associated with flagellin reception. FLS2 and FLS1 are different genes with different responsibilities, but are related genetically. FLS2 has a specific focus in plant defense and is involved in promoting the MAP kinase cascade. Mutations in the FLS2 gene can cause bacterial infection by lack of response to flg22. Therefore,FLS2’s primary focus is association with flg22 while its secondary focus is the involvement of promoting the MAP kinase cascade in plant defense.

<span class="mw-page-title-main">Brassinosteroid insensitive-1</span>

Brassinosteroid insensitive 1 (BRI1) is the major receptor of the plant hormone brassinosteroid. It plays very important roles in plant development, especially in the control of cell elongation and for the tolerance of environmental stresses. BRI1 enhances cell elongation, promotes pollen development, controls vasculature development and promotes chilling and freezing tolerance. BRI1 is one of the most well studied hormone receptors and it acts a model for the study of membrane-bound receptors in plants.

References

  1. 1 2 "Bacterial flagellin family". www.uniprot.org.
  2. ↑ "MeSH Browser". meshb.nlm.nih.gov. Retrieved 29 February 2024.
  3. ↑ Nedeljković M, Sastre DE, Sundberg EJ (July 2021). "Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure". Int J Mol Sci. 22 (14): 7521. doi: 10.3390/ijms22147521 . PMC   8306008 . PMID   34299141.
  4. 1 2 Steiner TS (February 2007). "How flagellin and toll-like receptor 5 contribute to enteric infection". Infection and Immunity. 75 (2): 545–52. doi:10.1128/IAI.01506-06. PMC   1828527 . PMID   17118981.
  5. ↑ Vonderviszt F, Keiichi N (2013). Structure, Function and Assembly of Flagellar Axial Proteins. Austin, TX: Madame Curie Bioscience Database.
  6. ↑ Maki-Yonekura S, Yonekura K, Namba K (April 2010). "Conformational change of flagellin for polymorphic supercoiling of the flagellar filament". Nature Structural & Molecular Biology. 17 (4): 417–22. doi:10.1038/nsmb.1774. PMID   20228803. S2CID   31915502.
  7. ↑ Imada K (April 2018). "Bacterial flagellar axial structure and its construction". Biophysical Reviews. 10 (2): 559–570. doi:10.1007/s12551-017-0378-z. PMC   5899737 . PMID   29235079.
  8. ↑ Samatey FA, Imada K, Nagashima S, Vonderviszt F, Kumasaka T, Yamamoto M, Namba K (March 2001). "Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling". Nature. 410 (6826): 331–7. Bibcode:2001Natur.410..331S. doi:10.1038/35066504. PMID   11268201. S2CID   4416455.
  9. ↑ Genta RM (January 1997). "The immunobiology of Helicobacter pylori gastritis". Seminars in Gastrointestinal Disease. 8 (1): 2–11. PMID   9000497.
  10. ↑ Sharma N, Akhade AS, Qadri A (April 2013). "Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells". Journal of Leukocyte Biology. 93 (4): 521–8. doi:10.1189/jlb.0712328. PMID   23345392. S2CID   21897008.
  11. ↑ Hatai H, Lepelley A, Zeng W, Hayden MS, Ghosh S (2016). "Toll-Like Receptor 11 (TLR11) Interacts with Flagellin and Profilin through Disparate Mechanisms". PLOS ONE. 11 (2): e0148987. Bibcode:2016PLoSO..1148987H. doi: 10.1371/journal.pone.0148987 . PMC   4747465 . PMID   26859749.
  12. ↑ DOI: 10.1126/sciimmunol.abq7001
  13. ↑ Kathrani A, Holder A, Catchpole B, Alvarez L, Simpson K, Werling D, Allenspach K (2012). "TLR5 risk-associated haplotype for canine inflammatory bowel disease confers hyper-responsiveness to flagellin". PLOS ONE. 7 (1): e30117. Bibcode:2012PLoSO...730117K. doi: 10.1371/journal.pone.0030117 . PMC   3261174 . PMID   22279566.
  14. ↑ García AV, Hirt H (2014-01-01). "Salmonella enterica induces and subverts the plant immune system". Frontiers in Microbiology. 5: 141. doi: 10.3389/fmicb.2014.00141 . PMC   3983520 . PMID   24772109.
  15. ↑ Gómez-Gómez L, Boller T (June 2000). "FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis". Molecular Cell. 5 (6): 1003–11. doi: 10.1016/S1097-2765(00)80265-8 . PMID   10911994.
  16. ↑ Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nürnberger T, Jones JD, Felix G, Boller T (July 2007). "A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence". Nature. 448 (7152): 497–500. Bibcode:2007Natur.448..497C. doi:10.1038/nature05999. hdl: 11858/00-001M-0000-0012-3840-F . PMID   17625569. S2CID   2818791.
  17. ↑ Urban, L.; Chabane Sari, D.; Orsal, B.; Lopes, M.; Miranda, R.; Aarrouf, J. (2018). "UV-C light and pulsed light as alternatives to chemical and biological elicitors for stimulating plant natural defenses against fungal diseases". Scientia Horticulturae . 235. Elsevier: 452–459. doi:10.1016/j.scienta.2018.02.057. ISSN   0304-4238. S2CID   90436989.
  18. ↑ Zipfel, Cyril; Robatzek, Silke; Navarro, Lionel; Oakeley, Edward J.; Jones, Jonathan D. G.; Felix, Georg; Boller, Thomas (April 2004). "Bacterial disease resistance in Arabidopsis through flagellin perception". Nature. 428 (6984): 764–767. Bibcode:2004Natur.428..764Z. doi:10.1038/nature02485. ISSN   0028-0836. PMID   15085136. S2CID   4332562.
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