Zh Zhou

© 2016, American Society for Biochemistry and Molecular Biology Inc. All rights reserved.Glycyl-tRNA synthetase is the enzyme that covalently links glycine to cognate tRNA for translation. It is of great research interest because of its nonconserved quaternary structures, unique species-specific aminoacylation properties, and noncanonical functions in neurological diseases, but none of these is fully understood. We report two crystal structures of human GlyRS variants, in the free form and in complex with tRNAGly respectively, and reveal new aspects of the glycylation mechanism. We discover that insertion 3 differs considerably in conformation in catalysis and that it acts like a "switch" and fully opens to allow tRNA to bind in a cross-subunit fashion. The flexibility of the protein is supported by molecular dynamics simulation, as well as enzymatic activity assays. The biophysical and biochemical studies suggest that human GlyRS may utilize its flexibility for both the traditional function and alternative functions.

This thesis presents a detailed investigation of Jaegwon’s Kim familiar analysis of events which holds that an event is the exemplification of a property by an object at a particular time. Despite its popularity across many areas of philosophy, the so-called Kimean view of events has been the subject of numerous criticisms, and is widely thought to be an implausible account of what events ontologically are. This thesis has two goals. First, I intend to relook at the common objections often thought to signal the death-knell of the Kimean view of events; I will argue that these objections are either unconvincing or that they may be easily circumvented. Second, by drawing from numerous seminal writings on the semantics and ontology of events by Zeno Vendler, I intend to argue that Kimean view of events presents a far too crude analysis of what events in fact are.

© 2014 Nature America, Inc. All rights reserved.Essential cellular processes involving the actin cytoskeleton are regulated by auxiliary proteins that can sense the nucleotide state of actin. Here we report cryo-EM structures for ADP-bound and ADP-beryllium fluoride -bound actin filaments in complex with the β-propeller domain of yeast coronin 1, at 8.6-Å resolution. Our structures reveal the main differences in the interaction of coronin with the two nucleotide states of F-actin. We derived pseudoatomic models by fitting the atomic structures of actin and coronin into the EM envelopes and confirmed the identified interfaces on actin by chemical cross-linking, fluorescence spectroscopy and actin mutagenesis. The models offer a structural explanation for the nucleotide-dependent effects of coronin on cofilin-assisted remodeling of F-actin.