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81.
Molecular chaperones and proteases monitor the folded state of other proteins. In addition to recognizing non-native conformations, these quality control factors distinguish substrates that can be refolded from those that need to be degraded. To investigate the molecular basis of this process, we have solved the crystal structure of DegP (also known as HtrA), a widely conserved heat shock protein that combines refolding and proteolytic activities. The DegP hexamer is formed by staggered association of trimeric rings. The proteolytic sites are located in a central cavity that is only accessible laterally. The mobile side-walls are constructed by twelve PDZ domains, which mediate the opening and closing of the particle and probably the initial binding of substrate. The inner cavity is lined by several hydrophobic patches that may act as docking sites for unfolded polypeptides. In the chaperone conformation, the protease domain of DegP exists in an inactive state, in which substrate binding in addition to catalysis is abolished. 相似文献
82.
Zusammenfassung Der Einfluss der Exstirpation von Bursa fabr. und Thymus junger Enten wurde zur Erklärung der Bedeutung dieser Organe für die Entwicklung der immunologischen Reaktivität untersucht. 相似文献
83.
On the possibility that thymus-mediated alloantigenic stimulation results in tolerance response 总被引:1,自引:0,他引:1
Résumé La tolérance de transplantation a été induite dans une combinaison antigéniquement faible du donneur et receveur par l'irradiation subléthale et le prétraitement antigénique spécifique chez la souris adulte. Les résultats obtenus sont compatibles avec l'idée que la fonction hypothétique du thymus lors du développement de l'autotolérance puisse jouer un rôle même dans la tolérance expérimentelle envers l'antigène étranger autant que cet antigène est permis d'entrer, sur quelque principe, dans le thymus. 相似文献
84.
Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination
Raya A Kawakami Y Rodríguez-Esteban C Ibañes M Rasskin-Gutman D Rodríguez-León J Büscher D Feijó JA Izpisúa Belmonte JC 《Nature》2004,427(6970):121-128
During vertebrate embryo development, the breaking of the initial bilateral symmetry is translated into asymmetric gene expression around the node and/or in the lateral plate mesoderm. The earliest conserved feature of this asymmetric gene expression cascade is the left-sided expression of Nodal, which depends on the activity of the Notch signalling pathway. Here we present a mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node. We identify the source of the asymmetric activation of Notch as a transient accumulation of extracellular calcium, which in turn depends on left-right differences in H+/K+-ATPase activity. Our results uncover a mechanism by which the Notch signalling pathway translates asymmetry in epigenetic factors into asymmetric gene expression around the node. 相似文献