A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.

Spore-forming pathogens like Clostridioides difficile depend on germination to initiate infection. During gemination, spores must degrade their cortex layer, which is a thick, protective layer of modified peptidoglycan. Cortex degradation depends on the presence of the spore-specific peptidoglycan m...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Carolina Alves Feliciano, Brian E Eckenroth, Oscar R Diaz, Sylvie Doublié, Aimee Shen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/2331f6a4fdfe4f99b4a48a7423afe147
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2331f6a4fdfe4f99b4a48a7423afe147
record_format	dspace
spelling	oai:doaj.org-article:2331f6a4fdfe4f99b4a48a7423afe1472021-12-02T20:03:18ZA lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.1553-73901553-740410.1371/journal.pgen.1009791https://doaj.org/article/2331f6a4fdfe4f99b4a48a7423afe1472021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009791https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Spore-forming pathogens like Clostridioides difficile depend on germination to initiate infection. During gemination, spores must degrade their cortex layer, which is a thick, protective layer of modified peptidoglycan. Cortex degradation depends on the presence of the spore-specific peptidoglycan modification, muramic-∂-lactam (MAL), which is specifically recognized by cortex lytic enzymes. In C. difficile, MAL production depends on the CwlD amidase and its binding partner, the GerS lipoprotein. To gain insight into how GerS regulates CwlD activity, we solved the crystal structure of the CwlD:GerS complex. In this structure, a GerS homodimer is bound to two CwlD monomers such that the CwlD active sites are exposed. Although CwlD structurally resembles amidase_3 family members, we found that CwlD does not bind Zn2+ stably on its own, unlike previously characterized amidase_3 enzymes. Instead, GerS binding to CwlD promotes CwlD binding to Zn2+, which is required for its catalytic mechanism. Thus, in determining the first structure of an amidase bound to its regulator, we reveal stabilization of Zn2+ co-factor binding as a novel mechanism for regulating bacterial amidase activity. Our results further suggest that allosteric regulation by binding partners may be a more widespread mode for regulating bacterial amidase activity than previously thought.Carolina Alves FelicianoBrian E EckenrothOscar R DiazSylvie DoubliéAimee ShenPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009791 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Carolina Alves Feliciano Brian E Eckenroth Oscar R Diaz Sylvie Doublié Aimee Shen A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.
description	Spore-forming pathogens like Clostridioides difficile depend on germination to initiate infection. During gemination, spores must degrade their cortex layer, which is a thick, protective layer of modified peptidoglycan. Cortex degradation depends on the presence of the spore-specific peptidoglycan modification, muramic-∂-lactam (MAL), which is specifically recognized by cortex lytic enzymes. In C. difficile, MAL production depends on the CwlD amidase and its binding partner, the GerS lipoprotein. To gain insight into how GerS regulates CwlD activity, we solved the crystal structure of the CwlD:GerS complex. In this structure, a GerS homodimer is bound to two CwlD monomers such that the CwlD active sites are exposed. Although CwlD structurally resembles amidase_3 family members, we found that CwlD does not bind Zn2+ stably on its own, unlike previously characterized amidase_3 enzymes. Instead, GerS binding to CwlD promotes CwlD binding to Zn2+, which is required for its catalytic mechanism. Thus, in determining the first structure of an amidase bound to its regulator, we reveal stabilization of Zn2+ co-factor binding as a novel mechanism for regulating bacterial amidase activity. Our results further suggest that allosteric regulation by binding partners may be a more widespread mode for regulating bacterial amidase activity than previously thought.
format	article
author	Carolina Alves Feliciano Brian E Eckenroth Oscar R Diaz Sylvie Doublié Aimee Shen
author_facet	Carolina Alves Feliciano Brian E Eckenroth Oscar R Diaz Sylvie Doublié Aimee Shen
author_sort	Carolina Alves Feliciano
title	A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.
title_short	A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.
title_full	A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.
title_fullStr	A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.
title_full_unstemmed	A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.
title_sort	lipoprotein allosterically activates the cwld amidase during clostridioides difficile spore formation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2331f6a4fdfe4f99b4a48a7423afe147
work_keys_str_mv	AT carolinaalvesfeliciano alipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT brianeeckenroth alipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT oscarrdiaz alipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT sylviedoublie alipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT aimeeshen alipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT carolinaalvesfeliciano lipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT brianeeckenroth lipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT oscarrdiaz lipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT sylviedoublie lipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation AT aimeeshen lipoproteinallostericallyactivatesthecwldamidaseduringclostridioidesdifficilesporeformation
_version_	1718375647499255808

A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.

Ejemplares similares