Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.
Proc Natl Acad Sci U S A
; 110(10): 3841-6, 2013 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-23431180
ABSTRACT
The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn(2+) sequestration. The asymmetry of the CP heterodimer creates a single Mn(2+)-binding site from six histidine residues, which distinguishes CP from all other Mn(2+)-binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn(2+) and Zn(2+) being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn(2+) sequestration. These data establish the importance of Mn(2+) sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo Antígeno L1 Leucocitário
/
Imunidade Inata
/
Manganês
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos