RESUMEN
In Escherichia coli, the master transcription regulator catabolite repressor activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that the E. coli enzyme fructose-1-kinase (FruK) can carry out its "reverse" reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a ΔfruK strain and fruK complementation show that FruK has a broader role in metabolism than fructose catabolism. Since fruK itself is repressed by Cra, these newly-reported events add layers to the dynamic regulation of E. coli's central metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK.
Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Fructoquinasas/metabolismo , Fructoquinasas/genética , Fructosa/metabolismo , Fructosadifosfatos/metabolismo , Fructosafosfatos/metabolismo , Regulación Bacteriana de la Expresión GénicaRESUMEN
KEY POINTS: Patients with traumatic brain injury (TBI) had worse olfactory quality of life (QoL) and Sino-Nasal Outcome Test-22 scores compared to a normal cohort. A worse olfactory QoL correlated with concussion symptom burden. Olfactory dysfunction among TBI patients should be addressed to improve overall outcomes.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Trastornos del Olfato , Calidad de Vida , Olfato , Humanos , Lesiones Traumáticas del Encéfalo/psicología , Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/complicaciones , Masculino , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/psicología , Trastornos del Olfato/etiología , Adulto , Femenino , Persona de Mediana Edad , Olfato/fisiología , Adulto Joven , Prueba de Resultado Sino-NasalRESUMEN
In Escherichia coli, the master transcription regulator Catabolite Repressor Activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that the E. coli enzyme fructose-1-kinase (FruK) can carry out its "reverse" reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a ΔfruK strain and fruK complementation show that FruK has a broader role in metabolism than fructose catabolism. The ΔfruK strain also alters biofilm formation. Since fruK itself is repressed by Cra, these newly-reported events add layers to the dynamic regulation of E. coli central metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK.
