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The Markey Scholars Conference: Proceedings
the OmpR/PhoB subfamily, the recognition helix is completely unobstructed by the regulatory domain.
The structure of DrrD suggests a model for regulation that is fundamentally different than that observed for other response regulators. Rather than a mechanism of regulation involving intra-molecular communication between the regulatory and effector domains within a monomer, the regulation within DrrD, and perhaps other members of the OmpR/PhoB subfamily, appears to occur through inter-molecular interactions. Specifically, activation is proposed to proceed primarily through dimerization of the phosphorylated regulatory domains with the effector domains participating as passive partners.
Chimeric response regulators within the OmpR/PhoB subfamily, involving the regulatory domain of one member attached to the effector domain of another, have been constructed and function well, providing further support for this type of mechanism. These experiments have been performed with a limited number of OmpR/PhoB subfamily members at this point. One of the questions that remains at this time is whether within the subfamily, all members will function by a similar regulatory mechanism or whether within this large family, different members will have different mechanisms of regulation.
This study has indicated that within large structural families, although sequence and structural similarity exist, there may be some very significant differences in the way proteins function and in particular, in the specific protein-protein interaction mechanisms that are being used for regulation in signal transduction proteins.
The people associated with studies of methylesterase CheB were Ganesh Anand, a graduate student who performed the biochemical analyses; and Ann West and Snezana Djordjevic, postdoctoral fellows who determined the structure. The deuterium exchange study was done in collaboration with Betsy Komives at UCSD. The people associated with analyses of the OmpR family transcription factors were Erik Martínez-Hackert and Patricia Harrison-McMonagle, graduate students who determined the structure of the DNA-binding domain and performed the cleavage analysis that allowed us to model the interaction with DNA; and David Buckler, a postdoctoral fellow who determined the structure of the intact OmpR family member, DrrD. Financial support was provided by the NIH and HHMI.