Structural basis for polyglutamate chain initiation and elongation by TTLL family enzymes

Glutamylation, introduced by TTLL enzymes, is the most abundant modification of brain tubulin. Essential effector proteins read the tubulin glutamylation pattern, and its misregulation causes neurodegeneration. TTLL glutamylases posttranslationally add glutamates to internal glutamates in tubulin C-terminal tails (branch initiation, through an isopeptide bond), and additional glutamates can extend these (elongation). TTLLs are thought to specialize for initiation or elongation, but the mechanistic basis for regioselectivity is unknown. We present cocrystal structures of murine TTLL6 bound to tetrahedral intermediate analogs that delineate key active-site residues that make this an elongase. We show that TTLL4 is exclusively an initiase, and through combined structural and phylogenetic analyses, engineer TTLL6 into a branch-initiating enzyme. TTLL glycylases add glycines posttranslationally to internal glutamates, and we find that the same active-site residues discriminate between initiase and elongase glycylases. These active-site specializations of TTLL glutamylases and glycylases ultimately yield the chemical complexity of cellular microtubules.

Predictive design of polymer molecular weight distributions in anionic polymerization

Polymer molecular weight distributions are targeted through kinetic modeled with high fidelity based on the temporal control of chain initiation in anionic polymerizations.

Chain initiation

This article describes the formation of the chemical electron paramagnetic resonance (EPR) spectroscopy institute established by Academician Vladislav V. Voevodsky (1917–1967) along with the history of the development of the instrumentation basis for this field of science in the Union of Soviet Socialist Republics (USSR). The design of the first EPR spectrometers for the chemical radio spectroscopy initiated the emergence of a new scientific instrumentation field in this country. Based on recollections shared by scientists and engineers and an examination of archive materials, the author reconstructs relevant events and identifies major participants in this process.