imported>Teaktl17: /* Relation to aging process */ fmt

2025-01-20T20:10:23Z

Relation to aging process: fmt

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{{cs1 config|name-list-style=vanc}}
{{Short description|Protein found in humans}}
{{infobox gene}}
'''Complement component 9''' ('''C9''') is a [[MACPF]] [[protein]] involved in the [[complement system]], which is part of the [[innate immune system]].<ref name="pmid7430628">{{cite journal | vauthors = Lint TF, Zeitz HJ, Gewurz H | title = Inherited deficiency of the ninth component of complement in man | journal = Journal of Immunology | volume = 125 | issue = 5 | pages = 2252–7 | date = November 1980 | doi = 10.4049/jimmunol.125.5.2252 | pmid = 7430628 | url = http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7430628 | doi-access = free }}</ref> Once activated, about 12-18 molecules of C9 polymerize to form pores in target [[Cell membrane|cell membranes]], causing [[lysis]] and cell death.<ref name = "Dudkina_2016">{{cite journal | vauthors = Dudkina NV, Spicer BA, Reboul CF, Conroy PJ, Lukoyanova N, Elmlund H, Law RH, Ekkel SM, Kondos SC, Goode RJ, Ramm G, Whisstock JC, Saibil HR, Dunstone MA | display-authors = 6 | title = Structure of the poly-C9 component of the complement membrane attack complex | journal = Nature Communications | volume = 7 | issue = 1 | pages = 10588 | date = February 2016 | pmid = 26841934 | pmc = 4742998 | doi = 10.1038/ncomms10588 | bibcode = 2016NatCo...710588D }}</ref> C9 is one member of the [[complement membrane attack complex]] (MAC), which also includes complement components [[Complement component 5|C5b]], [[Complement component 6|C6]], [[Complement component 7|C7]] and [[C8 complex|C8]].<ref name="Mohapatra_2020">{{Cite journal| vauthors = Mohapatra A, Das S, Dey S, Sahoo PK |date= April 2020 |title=Molecular characterization and induced expression analysis of the terminal complement component C9 in rohu, Labeo rohita |journal=Aquaculture Research|language=en|volume=51|issue=4|pages=1415–1427|doi=10.1111/are.14487|s2cid= 213565293 |issn=1355-557X|doi-access=free}}</ref><ref name="Spicer_2018">{{cite journal | vauthors = Spicer BA, Law RH, Caradoc-Davies TT, Ekkel SM, Bayly-Jones C, Pang SS, Conroy PJ, Ramm G, Radjainia M, Venugopal H, Whisstock JC, Dunstone MA | display-authors = 6 | title = The first transmembrane region of complement component-9 acts as a brake on its self-assembly | journal = Nature Communications | volume = 9 | issue = 1 | pages = 3266 | date = August 2018 | pmid = 30111885 | pmc = 6093860 | doi = 10.1038/s41467-018-05717-0 | bibcode = 2018NatCo...9.3266S }}</ref><ref>{{cite journal | vauthors = Wickramaarachchi WD, Wan Q, Lee Y, Lim BS, De Zoysa M, Oh MJ, Jung SJ, Kim HC, Whang I, Lee J | display-authors = 6 | title = Genomic characterization and expression analysis of complement component 9 in rock bream (Oplegnathus fasciatus) | journal = Fish & Shellfish Immunology | volume = 33 | issue = 4 | pages = 707–17 | date = October 2012 | pmid = 22796422 | doi = 10.1016/j.fsi.2012.06.019 }}</ref> The formation of the MAC occurs through three distinct pathways: the classical, alternative, and lectin pathways.<ref name="Mohapatra_2020" /> Pore formation by C9 is an important way that bacterial cells are killed during an infection, and the target cell is often covered in multiple MACs. The clinical impact of a deficiency in C9 is an infection with the gram-negative bacterium ''[[Neisseria meningitidis]].''<ref name="Fu_2016">{{cite journal | vauthors = Fu X, Ju J, Lin Z, Xiao W, Li X, Zhuang B, Zhang T, Ma X, Li X, Ma C, Su W, Wang Y, Qin X, Liang S | display-authors = 6 | title = Target deletion of complement component 9 attenuates antibody-mediated hemolysis and lipopolysaccharide (LPS)-induced acute shock in mice | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 30239 | date = July 2016 | pmid = 27444648 | pmc = 4957234 | doi = 10.1038/srep30239 | bibcode = 2016NatSR...630239F }}</ref>

== Structure ==
C9 genes include 11 [[Exon|exons]] and 10 [[Intron|introns]] when found in fish.<ref name="Li_2007">{{cite journal | vauthors = Li L, Chang MX, Nie P | title = Molecular cloning, promoter analysis and induced expression of the complement component C9 gene in the grass carp Ctenopharyngodon idella | journal = Veterinary Immunology and Immunopathology | volume = 118 | issue = 3–4 | pages = 270–82 | date = August 2007 | pmid = 17604124 | doi = 10.1016/j.vetimm.2007.05.005 }}</ref> In fish, the liver is the site where the majority of complement components are produced and expressed, but C9 can also be found in other tissues.<ref name="Li_2007" /> It is a single-chain glycoprotein with a four domain structure arranged in a globular bundle.<ref name="Fu_2016" /><ref name="Li_2007" />

== Pore formation ==
MAC formation starts with the assembly of a tetrameric complex with the complement components C6, C7, C8, and C5b.<ref>{{Cite journal| vauthors = Fu YW, Zhu CK, Zhang QZ |date= May 2019 |title=Molecular characterization and expression analysis of complement components C3 and C9 in largemouth bronze gudgeon (Coreius guichenoti) in response to Ichthyophthirius multifiliis infection|journal=Aquaculture|language=en|volume=506|pages=270–279|doi=10.1016/j.aquaculture.2019.03.046|bibcode= 2019Aquac.506..270F |s2cid= 133378035 }}</ref> The final step of MAC on target cell surfaces involves the polymerization of C9 molecules bound to C5b8 forming C5b-9.<ref name="Spicer_2018" /><ref name="Fu_2016" /><ref name = "Li_2007" /> C9 molecules allow cylindrical, asymmetrical transmembrane pores to form. The overall complex belongs to MAC/perforin-like (MACPF)/CDC superfamily.<ref name = "Dudkina_2016" /> Pore formation involves binding the C9 molecules to the target membrane, membrane molecules forming a pre-pore shape, and conformational change in the TMH1, the first transmembrane region, and TMH2, the second transmembrane region.<ref name="Spicer_2018" /> The formations of pores leads to the killing of foreign pathogens and infected host cells.

== Relation to aging process ==
C9 was found to be the most strongly under expressed serum protein in men who achieved longevity, compared to men who did not.<ref>{{Cite journal| vauthors = Orwoll E, Wiedrick J, Nielson C, etal | title = Proteomic assessment of serum biomarkers of longevity in older men | journal = Aging Cell| year = 2020 | volume = 19 | issue = 11 | pages = e13253 |language=en|doi=10.1111/acel.13253| pmid = 33078901 |pmc=7681066 | doi-access = free}}</ref>

== References ==
{{Reflist}}

== External links ==
* {{MeshName|Complement+9}}
* [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P02748 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Complement component C9

{{Complement system}}

[[Category:Complement system]]

{{immunology-stub}}

Complement component 9 - Revision history

imported>Teaktl17: /* Relation to aging process */ fmt