Long Chen

© 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.

Despite his unreserved appreciation of Turing’s analysis for being a “precise and unquestionably adequate definition” of formal system or mechanical computability, Gödel nevertheless published a short note in 1972 claiming to have found a “philosophical error” in Turing’s argument with regard to the finite nature of mental states and memory. A natural question arises: how could Gödel enjoy the generality conferred on his results by Turing’s work, despite the error of its ways? Previous interpretative strategies by Feferman, Shagrir and others have mainly tried to resolve the disparity by distinguishing different types of arguments in Turing and taking Gödel to approve only some of them. By a more integral examination of their ideas, especially Turing’s response to the “mathematical objection” based on Gödel’s incompleteness theorem and Gödel’s own conception of finite yet non-mechanical procedures, and taking some of the main ideas of current developments in machine learning into consideration, I will try to present a new explanation for the apparent disparity, arguing that there is no “error” on Turing’s side and the seemingly conflicting views held by Turing and Gödel should best be seen as complementary, keeping intuition and ingenuity together.