http://debianws.lexgopc.com/wiki143/index.php?action=history&feed=atom&title=Complement_membrane_attack_complexComplement membrane attack complex - Revision history2026-05-01T17:40:06ZRevision history for this page on the wikiMediaWiki 1.43.1http://debianws.lexgopc.com/wiki143/index.php?title=Complement_membrane_attack_complex&diff=1195402&oldid=previmported>YuniToumei: restructure article: rm duplicate reflist before Pathology paragraph2024-12-30T08:12:29Z<p>restructure article: rm duplicate reflist before Pathology paragraph</p>
<p><b>New page</b></p><div>{{Short description|Protein complex}}<br />
{{see also|MACPF}}<br />
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[[Image:Membrane Attack Complex (Terminal Complement Complex C5b-9).png|thumb|right|Membrane attack complex (Terminal complement complex C5b-9)]]<br />
[[Image:complement death.PNG|thumb|right|A membrane attack complex attached to a pathogenic cell]]<br />
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The '''membrane attack complex''' ('''MAC''') or '''terminal complement complex''' ('''TCC''') is a complex of proteins typically formed on the surface of [[pathogen]] [[cell membrane]]s as a result of the activation of the host's [[complement system]], and as such is an effector of the [[immune system]]. [[Antibody]]-mediated complement activation leads to MAC deposition on the surface of infected cells.<ref name="pmid32194049">{{cite journal | vauthors = Xie CB, Jane-Wit D, Pober JS | title = Complement Membrane Attack Complex: New Roles, Mechanisms of Action, and Therapeutic Targets | journal = [[The American Journal of Pathology]] | volume = 190 | issue=6 | pages = 1138–1150 | date=2020 | doi = 10.1016/j.ajpath.2020.02.006 | pmc=7280757 | pmid = 32194049}}</ref> Assembly of the MAC leads to pores that disrupt the [[cell membrane]] of target cells, leading to cell [[lysis]] and death.<ref name="Janeway 2001">{{cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK27100|title=The complement system and innate immunity|last=Janeway|first=CA Jr|author2=Travers P|author3=Walport M|year=2001|work=Immunobiology: The Immune System in Health and Disease|publisher=Garland Science|access-date=4 January 2018|location=New York|display-authors=etal}}</ref><br />
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The MAC is composed of the complement components [[complement component 5|C5b]], [[complement component 6|C6]], [[complement component 7|C7]], [[C8 complex|C8]] and several [[complement component 9|C9]] molecules.<br />
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A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-6-7-8 complex. C5b-6-7-8 subsequently binds to C9<ref name="PUB00000295">{{cite journal |doi=10.1021/bi00417a050 |vauthors=Stanley KK, Marazziti D, Eggertsen G, Fey GH |title=Relationships between the gene and protein structure in human complement component C9 |journal=Biochemistry |volume=27 |issue=17 |pages=6529–6534 |year=1988 |pmid=3219351}}</ref><ref name="PUB00001141">{{cite journal |author=Stanley KK|author2=Luzio JP|author3=Tschopp J|author-link3=Jürg Tschopp|author4=Kocher HP|author5=Jackson P |title=The sequence and topology of human complement component C9 |journal=EMBO J. |volume=4 |issue=2 |pages=375–382 |year=1985 |doi=10.1002/j.1460-2075.1985.tb03639.x |pmid=4018030 |pmc=554196}}</ref><ref name="PUB00004608">{{cite journal |doi=10.1073/pnas.81.23.7298 |vauthors=Fey GH, Hugli TE, Podack ER, Gehring MR, Kan CC, DiScipio RG |title=Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=81 |issue=23 |pages=7298–7302 |year=1984 |pmid=6095282 |pmc=392133|bibcode=1984PNAS...81.7298D |doi-access=free }}</ref> and acts as a catalyst in the polymerization of C9.<br />
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==Structure and function==<br />
MAC is composed of a complex of four complement [[protein]]s (C5b, C6, C7, and C8) that bind to the outer surface of the [[plasma membrane]], and many copies of a fifth protein (C9) that hook up to one another, forming a ring in the membrane. C6-C9 all contain a common [[MACPF]] domain.<ref>{{cite journal |vauthors=Tschopp J, Masson D, Stanley KK |title=Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis |journal=Nature |volume=322 |issue=6082 |pages=831–4 |year=1986 |pmid=2427956 |doi=10.1038/322831a0|bibcode=1986Natur.322..831T |s2cid=4330219 }}</ref> This region is [[Homology (biology)|homologous]] to cholesterol-dependent [[cytolysin]]s from Gram-positive bacteria.<ref name="macpfstructure">{{cite journal |author=Carlos J. Rosado |author2=Ashley M. Buckle |author3=Ruby H. P. Law|author4=Rebecca E. Butcher |author5=Wan-Ting Kan|author6=Catherina H. Bird |author7=Kheng Ung|author8=Kylie A. Browne |author9=Katherine Baran|author10=Tanya A. Bashtannyk-Puhalovich |author11=Noel G. Faux |author12=Wilson Wong |author13=Corrine J. Porter |author14=Robert N. Pike |author15=Andrew M. Ellisdon|author16=Mary C. Pearce |author17=Stephen P. Bottomley |author18=Jonas Emsley |author19=A. Ian Smith |author20=Jamie Rossjohn |author21=Elizabeth L. Hartland |author22=Ilia Voskoboinik |author23=Joseph A. Trapani |author24=Phillip I. Bird |author25=Michelle A. Dunstone |author26=James C. Whisstock |name-list-style=amp |title=A Common Fold Mediates Vertebrate Defense and Bacterial Attack |journal=Science |year=2007 |pmid= 17717151 |doi=10.1126/science.1144706 |volume=317 |pages=1548–51 |issue=5844|bibcode=2007Sci...317.1548R |s2cid=20372720 |doi-access=free }}</ref><br />
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The ring structure formed by C9 is a pore in the membrane that allows free [[diffusion]] of molecules in and out of the cell. If enough pores form, the cell is no longer able to survive.<br />
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If the pre-MAC complexes of C5b-7, C5b-8 or C5b-9 do not insert into a membrane, they can form inactive complexes with [[Protein S]] (sC5b-7, sC5b-8 and sC5b-9). These fluid phase complexes do not bind to cell membranes and are ultimately scavenged by [[clusterin]] and [[vitronectin]], two regulators of complement.<ref>{{cite journal|last1=Hadders|first1=MA|title=Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9|journal=Cell Rep|date=2012|volume=1|issue=3|doi=10.1016/j.celrep.2012.02.003|pmc=3314296|pmid=22832194|pages=200–207}}</ref><br />
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==Initiation: C5-C7==<br />
[[File:Formowanie MAC-en.svg|thumb|350px|right|Membrane attack complex]]<br />
The membrane attack complex is initiated when the complement protein [[C5 convertase]] cleaves [[Complement component 5|C5]] into C5a and C5b. All three pathways of the complement system ([[Classical complement pathway|classical]], [[lectin pathway|lectin]] and [[Alternative complement pathway|alternative]] pathways) initiate the formation of MAC.<br />
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Another complement protein, [[Complement component 6|C6]], binds to C5b.<br />
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The C5bC6 complex is bound by [[Complement component 7|C7]].<br />
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This junction alters the configuration of the protein molecules exposing a hydrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen.<br />
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==Polymerization: C8-C9==<br />
Similar hydrophobic sites on [[C8 complex|C8]] and [[Complement component 9|C9]] molecules are exposed when they bind to the complex, so they can also insert into the bilayer.<br />
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C8 is a complex made of the two proteins C8-beta and C8 alpha-gamma.<br />
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C8 alpha-gamma has the hydrophobic area that inserts into the bilayer. C8 alpha-gamma induces the polymerization of 10-16 molecules of C9 into a pore-forming structure known as the membrane attack complex.<ref name="Janeway 2001" /><br />
* MAC has a [[hydrophobic]] ''external face'' allowing it to associate with the [[lipid bilayer]].<br />
* MAC has a [[hydrophilic]] ''internal face'' to allow the passage of water.<br />
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Multiple molecules of C9 can join spontaneously in concentrated solution to form polymers of C9. These polymers can also form a tube-like structure.<br />
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==Inhibition==<br />
[[CD59]] acts to inhibit the complex. This exists on body cells to protect them from MAC.<br />
A rare condition, [[paroxysmal nocturnal haemoglobinuria]], results in red blood cells that lack CD59. These cells can, therefore, be lysed by MAC. Inhibition of MAC has been shown to reduce inflammation and neuroaxonal loss at 72 hours post-Traumatic Brain Injury (TBI) event, potentially preventing neurological damage, especially in cases with acquired sepsis or respiratory failure.<ref>Fluiter, K., Opperhuizen, A. L., Morgan, B. P., Baas, F., & Ramaglia, V. (2014). Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. The Journal of Immunology, 192(5), 2339–2348. https://doi.org/10.4049/jimmunol.1302793</ref><br />
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==Pathology==<br />
Deficiencies of C5 to C9 components do not lead to a generalized susceptibility to infections but only to an increased susceptibility to ''[[Neisseria]]'' infections,<ref>Ronald Hoffman, Leslie E. Silberstein, Helen Heslop, Jeffrey Weitz, ''Hematology: Basic Principles and Practice'', 6th ed., Elsevier, 2013, [https://books.google.com/books?id=a1estSuaQ6kC&pg=PA231 page 231].</ref> since ''Neisseria'' have a thin [[cell wall]] and little to no [[glycocalyx]].<ref>{{cite book |last1=Abbas |first1=Abul K. |title=Basic Immunology: Functions and Disorders of the Immune System |date=2020 |publisher=Elsevier |location=Philadelphia, PA |isbn=978-0-323-54943-1 |pages=158–176 |edition=6th}}</ref><br />
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==See also==<br />
* [[Terminal complement pathway deficiency]]<br />
* [[Paroxysmal nocturnal haemoglobinuria]]<br />
* [[Perforin]]<br />
* [[Pore-forming toxin]]<br />
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==References==<br />
{{reflist}}<br />
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==External links==<br />
* {{Commonscatinline}}<br />
* {{MeshName|Complement+Membrane+Attack+Complex}}<br />
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{{Complement system}}<br />
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[[Category:Complement system]]<br />
[[Category:Immune system]]<br />
[[Category:Immunology]]</div>imported>YuniToumei