Biomedical subjects

James Z Chadick

Publications and source records attributed to James Z Chadick.

3 recordsLinked to original sources

PubMed2005

Preponderance of free mediator in the yeast Saccharomyces cerevisiae.

Biochemical evidence suggesting that the predominant form of Mediator in the yeast Saccharomyces cerevisiae might be one in which the complex is associated with RNA polymerase II to form a holoenzyme has led to the proposition of a holoenzyme-based model for transcription initiation. We report that polymerase-free Mediator, isolated early on during a whole-cell extract fractionation protocol, is in fact the most abundant form of the Mediator complex. The existence of free Mediator would make possible independent recruitment of Mediator and RNA polymerase II to the pre-initiation complex. This is in agreement with reports from in vivo studies of time and spatial independence of Mediator and RNA polymerase II promoter interaction, with current models of pre-initiation complex structure in which promoter DNA upstream of the transcription start site is positioned between Mediator and polymerase, and with the proposed role of Mediator as the major component of the Scaffold complex involved in transcription reinitiation.

Cell Fractionation↗

PubMed2005

Structure and molecular organization of mammalian fatty acid synthase.

De novo synthesis of fatty acids in the cytosol of animal cells is carried out by the multifunctional, homodimeric fatty acid synthase (FAS). Cryo-EM analysis of single FAS particles imaged under conditions that limit conformational variability, combined with gold labeling of the N termini and structural analysis of the FAS monomers, reveals two coiled monomers in an overlapping arrangement. Comparison of dimeric FAS structures related to different steps in the fatty acid synthesis process indicates that only limited local rearrangements are required for catalytic interaction among different functional domains. Monomer coiling probably contributes to FAS efficiency and provides a structural explanation for the reported activity of a FAS monomer dimerized to a catalytically inactive partner. The new FAS structure provides a new paradigm for understanding the architecture of FAS and the related modular polyketide synthases.

Animals↗

PubMed2005

Structure of eukaryotic Mediator complexes.

Mediator, a macromolecular complex comprising approximately 20 different protein components, is largely responsible for the tight control of transcription that underpins cell development, differentiation, and maintenance in eukaryotes from yeast to human. In the past five years, macromolecular electron microscopy has been used to characterize the structure of Mediator, and of the complexes it forms with other components of the transcription machinery. The results reveal how Mediator interacts with RNA polymerase II, and suggest that regulatory information could be conveyed through changes in Mediator conformation that would influence the transcription initiation process.

Animals↗