RESUMEN
A common theme in bacterial disease is the manipulation of the eukaryotic cytoskeleton by pathogenic factors. Understanding how virulence factors operate to achieve these alterations is a growing and important research effort. This review focuses on several virulence factors from the pathogen Salmonella, and considers the contributions of structural biology to our appreciation of bacterial modulation of cytoskeletal dynamics.
Asunto(s)
Proteínas Bacterianas/metabolismo , Salmonella/patogenicidad , Factores de Virulencia/metabolismo , Animales , Proteínas Bacterianas/química , Citoesqueleto/metabolismo , Humanos , Modelos Moleculares , Transporte de Proteínas , Salmonella/metabolismo , Factores de Virulencia/química , Proteínas de Unión al GTP rho/química , Proteínas de Unión al GTP rho/metabolismoRESUMEN
A critical molecular interaction during assembly of the major histocompatibility complex (MHC) class I molecules takes place between the heavy chain and the transporter-associated with antigen-processing (TAP) complex. The recent mapping of regions of the heavy chain involved in the binding to TAP suggests a complex molecular interaction essential for the cell surface expression of the MHC class I. The advances made in understanding the TAP-MHC class I interaction are reviewed and discussed here.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antígenos de Histocompatibilidad Clase I/química , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2 , Transportadoras de Casetes de Unión a ATP/química , Alelos , Presentación de Antígeno , Citosol/metabolismo , Dimerización , Retículo Endoplásmico/metabolismo , Antígenos de Histocompatibilidad Clase I/fisiología , HumanosRESUMEN
Cytotoxicity is a major effector function of CD8(+) T cells. Although mitogen-activated protein kinase (MAP kinase) / extracellular regulatory kinase (ERK) activity is indispensable for cytotoxic activity of most CD8(+) T cells a portion of CD8(+) T cells appears resistant to MEK inhibition as cytotoxicity of bulk cultures was partially preserved in the presence of a MEK inhibitor. We have also identified a long-term CD8(+) T cell line with unaltered cytolytic activity after prevention of ERK activation. Antigen-induced microtubule organizing center (MTOC) reorientation was not prevented in this CD8(+) cell line by MEK inhibition, in sharp contrast to the MTOC reorientation prevention in a CD8(+) T cell clone with MEK inhibition-sensitive cytolytic activity. These findings suggest that resistance of lysis to MEK inhibition may be due to a lack of ERK control over MTOC reorientation in some CD8(+) T cells. Thus, there appears to be a heterogeneity of ERK-regulated cytolytic activity in CD8(+) T cells, most likely resulting from a differential control of ERK over MTOC motility.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Citotoxicidad Inmunológica , Sistema de Señalización de MAP Quinasas/inmunología , Proteínas Quinasas Activadas por Mitógenos/inmunología , Transducción de Señal/inmunología , Animales , Antígenos CD8/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
In previous studies we demonstrated that mutations in the genes cysB, cysE, and cls (nov) affect resistance of Escherichia coli to novobiocin (J. Rakonjac, M. Milic, and D. J. Savic, Mol. Gen. Genet. 228:307-311, 1991; R. Ivanisevic, M. Milic, D. Ajdic, J. Rakonjac, and D. J. Savic, J. Bacteriol. 177:1766-1771, 1995). In this work we expand this list with mutations in rpoN (the gene for RNA polymerase subunit sigma54) and the tRNA synthetase genes alaS, argS, ileS, and leuS. Similarly to resistance to the penicillin antibiotic mecillinam, resistance to novobiocin of tRNA synthetase mutants appears to depend upon the RelA-mediated stringent response. However, at this point the overlapping pathways of mecillinam and novobiocin resistance diverge. Under conditions of stringent response induction, either by the presence of tRNA synthetase mutations or by constitutive production of RelA protein, inactivation of the cls gene diminishes resistance to novobiocin but not to mecillinam.