The molecular chaperonins are essential proteins involved in protein folding, complex assembly, and polypeptide translocation. While there is abundant structural information about the machinery and the mechanistic details of its action are well studied, it is yet unresolved how chaperonins recognize a large number of structurally unrelated polypeptides in their unfolded or partially folded forms. To determine the nature of chaperonin-substrate recognition, we have characterized by NMR methods the interactions of GroEL with synthetic peptides that mimic segments of unfolded proteins. In previous work, we found using transferred nuclear Overhauser effect (trNOE) analysis that two 13 amino acid peptides bound GroEL in an amphipathic alpha-helical conformation. By extending the study to a variety of peptides with differing sequence motifs, we have observed that peptides can adopt conformations other than alpha-helix when bound to GroEL. Furthermore, peptides of the same composition exhibited significantly different affinities for GroEL as manifested by the magnitude of trNOEs. Binding to GroEL correlates well with the ability of the peptide to cluster hydrophobic residues on one face of the peptide, as determined by the retention time on reversed-phase (RP) HPLC. We conclude that the molecular basis of GroEL-substrate recognition is the presentation of a hydrophobic surface by an incompletely folded polypeptide and that many backbone conformations can be accommodated.
Self-regulation is a concept from the field of developmental psychology that describes a person's ability to generate socially approved behauior in the absence of external monitors. It is considered to be a significant aspect in the socialization of children. School-based mediation programs that train students in communication and problemsolving skills and allow them to practice these skills, can be a n asset to schools in a number of ways. Mediation is an effective way of addressing discipline problems that are especially difficult to handle using traditional means. At the same time, students participating in a mediation program are rehearsed in skills that lead t o selfregulation.
Mediation is frequently mandated as a first step for custody, visitation, and divorce cases. As a process that requires a balance of power between participants, mediation is not an appropriate method to resolve domestic violence disputes, a phenomenon that reflects profound disparities in power between the perpetrator and the victim. Of all marriages referred to court‐based divorce and custody/visitation mediation programs, 50% to 80% involve domestic violence. This raises very serious questions about mandatory mediation. This article considers the effects of domestic violence on the mediation process. It questions the use of mandatory mediation and suggests ways that mediators might recognize and respond to domestic violence.
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