Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.

α(2) macroglobulins (α(2)Ms) are broad-spectrum protease inhibitors that play essential roles in the innate immune system of eukaryotic species. These large, multi-domain proteins are characterized by a broad-spectrum bait region and an internal thioester, which, upon cleavage, becomes covalently as...

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Autores principales:	David Neves, Leandro F Estrozi, Viviana Job, Frank Gabel, Guy Schoehn, Andréa Dessen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29a3ebb461c4455c9236a40b58ce2f97
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spelling	oai:doaj.org-article:29a3ebb461c4455c9236a40b58ce2f972021-11-18T07:21:55ZConformational states of a bacterial α2-macroglobulin resemble those of human complement C3.1932-620310.1371/journal.pone.0035384https://doaj.org/article/29a3ebb461c4455c9236a40b58ce2f972012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22530012/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203α(2) macroglobulins (α(2)Ms) are broad-spectrum protease inhibitors that play essential roles in the innate immune system of eukaryotic species. These large, multi-domain proteins are characterized by a broad-spectrum bait region and an internal thioester, which, upon cleavage, becomes covalently associated to the target protease, allowing its entrapment by a large conformational modification. Notably, α(2)Ms are part of a larger protein superfamily that includes proteins of the complement system, such as C3, a multi-domain macromolecule which is also characterized by an internal thioester-carrying domain and whose activation represents the pivotal step in the complement cascade. Recently, α(2)M/C3-like genes were identified in a large number of bacterial genomes, and the Escherichia coli α(2)M homolog (ECAM) was shown to be activated by proteases. In this work, we have structurally characterized ECAM by electron microscopy and small angle scattering (SAXS) techniques. ECAM is an elongated, flexible molecule with overall similarities to C3 in its inactive form; activation by methylamine, chymotrypsin, or elastase induces a conformational modification reminiscent of the one undergone by the transformation of C3 into its active form, C3b. In addition, the proposed C-terminus of ECAM displays high flexibility and different conformations, and could be the recognition site for partner macromolecules. This work sheds light on a potential bacterial defense mechanism that mimics structural rearrangements essential for activation of the complement cascade in eukaryotes, and represents a possible novel target for the development of antibacterials.David NevesLeandro F EstroziViviana JobFrank GabelGuy SchoehnAndréa DessenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35384 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Neves Leandro F Estrozi Viviana Job Frank Gabel Guy Schoehn Andréa Dessen Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.
description	α(2) macroglobulins (α(2)Ms) are broad-spectrum protease inhibitors that play essential roles in the innate immune system of eukaryotic species. These large, multi-domain proteins are characterized by a broad-spectrum bait region and an internal thioester, which, upon cleavage, becomes covalently associated to the target protease, allowing its entrapment by a large conformational modification. Notably, α(2)Ms are part of a larger protein superfamily that includes proteins of the complement system, such as C3, a multi-domain macromolecule which is also characterized by an internal thioester-carrying domain and whose activation represents the pivotal step in the complement cascade. Recently, α(2)M/C3-like genes were identified in a large number of bacterial genomes, and the Escherichia coli α(2)M homolog (ECAM) was shown to be activated by proteases. In this work, we have structurally characterized ECAM by electron microscopy and small angle scattering (SAXS) techniques. ECAM is an elongated, flexible molecule with overall similarities to C3 in its inactive form; activation by methylamine, chymotrypsin, or elastase induces a conformational modification reminiscent of the one undergone by the transformation of C3 into its active form, C3b. In addition, the proposed C-terminus of ECAM displays high flexibility and different conformations, and could be the recognition site for partner macromolecules. This work sheds light on a potential bacterial defense mechanism that mimics structural rearrangements essential for activation of the complement cascade in eukaryotes, and represents a possible novel target for the development of antibacterials.
format	article
author	David Neves Leandro F Estrozi Viviana Job Frank Gabel Guy Schoehn Andréa Dessen
author_facet	David Neves Leandro F Estrozi Viviana Job Frank Gabel Guy Schoehn Andréa Dessen
author_sort	David Neves
title	Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.
title_short	Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.
title_full	Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.
title_fullStr	Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.
title_full_unstemmed	Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.
title_sort	conformational states of a bacterial α2-macroglobulin resemble those of human complement c3.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/29a3ebb461c4455c9236a40b58ce2f97
work_keys_str_mv	AT davidneves conformationalstatesofabacteriala2macroglobulinresemblethoseofhumancomplementc3 AT leandrofestrozi conformationalstatesofabacteriala2macroglobulinresemblethoseofhumancomplementc3 AT vivianajob conformationalstatesofabacteriala2macroglobulinresemblethoseofhumancomplementc3 AT frankgabel conformationalstatesofabacteriala2macroglobulinresemblethoseofhumancomplementc3 AT guyschoehn conformationalstatesofabacteriala2macroglobulinresemblethoseofhumancomplementc3 AT andreadessen conformationalstatesofabacteriala2macroglobulinresemblethoseofhumancomplementc3
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Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.

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