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Molecular descriptions of intrinsically disordered protein regions (IDRs) are fundamental to understanding their cellular functions and regulation. NMR spectroscopy has been a leading tool in characterizing IDRs at the atomic level. In this review, we highlight recent conceptual breakthroughs in the study of IDRs facilitated by NMR and discuss emerging NMR techniques that bridge molecular descriptions to cellular functions. First, we review the assemblies formed by IDRs at various scales, from one-to-one complexes to non-stoichiometric clusters and condensates, discussing how NMR characterizes their structural dynamics and molecular interactions. Next, we explore several unique interaction modes of IDRs that enable regulatory mechanisms such as selective transport and switch-like inhibition. Finally, we highlight recent progress in solid-state NMR and in-cell NMR on IDRs, discussing how these methods allow for atomic characterization of full-length IDR complexes in various phases and cellular environments. This review emphasizes recent conceptual and methodological advancements in IDR studies by NMR and offers future perspectives on bridging the gap between in vitro molecular descriptions and the cellular functions of IDRs. 

Intrinsically disordered proteins are frequent targets for functional regulation through post-translational modification due to their high accessibility to modifying enzymes and the strong influence of changes in primary structure on their chemical properties. While lysine N ε -acetylation was first observed as a common modification of histone tails, proteomic data suggest that lysine acetylation is ubiquitous among both nuclear and cytosolic proteins. However, compared with our biophysical understanding of the other common post-translational modifications, mechanistic studies to document how lysine N ε -acetyl marks are placed, utilized to transduce signals, and eliminated when signals need to be turned off, have not kept pace with proteomic discoveries. Herein we report a nuclear magnetic resonance method to monitor N ε -lysine acetylation through enzymatic installation of a 13 C-acetyl probe on a protein substrate, followed by detection through 13 C direct-detect spectroscopy. We demonstrate the ease and utility of this method using histone H3 tail acetylation as a model. The clearest advantage to this method is that it requires no exogenous tags that would otherwise add steric bulk, change the chemical properties of the modified lysine, or generally interfere with downstream biochemical processes. The non-perturbing nature of this tagging method is beneficial for application in any system where changes to local structure and chemical properties beyond those imparted by lysine modification are unacceptable, including intrinsically disordered proteins, bromodomain containing protein complexes, and lysine deacetylase enzyme assays. 

Maximizing ion conduction in single-ion-conducting ionomers is essential for their application in energy-related technologies such as Li-ion batteries. Understanding the anion chemical composition impacts on ion conduction offers new perspectives to maximize ion transport, since the current approach of lowering T g has apparently reached a limit (lowest T g ∼ 190 K, highest conductivity ∼10 −5 –10 −4 S cm −1 ). Here, a series of random ionomers are synthesized by copolymerizing poly(ethylene glycol)methacrylate with either sulfonylimide lithium methacrylate (MTLi) or sulfonate lithium methacrylate (MSLi) using reversible addition–fragmentation chain transfer (RAFT) polymerization. Li-Ion conduction and self-diffusion coefficients ( D Li + ) of the ionomers are characterized with dielectric relaxation spectroscopy (DRS) and pulsed-field-gradient (PFG) NMR diffusometry, respectively. Increasing ion content decreases the Li-ion conductivity and D Li + , as expected from the increased T g . Moreover, a considerably lower ionic conductivity and D Li + are observed for MSLi compared to MTLi at constant ion content and T g / T . As revealed from X-ray scattering, strong ion aggregation in MSLi results in much lower conductivity and D Li + compared with less aggregated MTLi based on the more delocalized sulfonylimide anion. These results emphasize the detrimental and molecularly specific role of ion aggregation in Li-ion conductivity, and highlight the necessity for minimizing ion aggregation via the rational choice of anion chemical composition. 

Abstract Although the interactions among glass formers and modifiers, for example, connectivity and charge distribution, have been studied extensively in oxide glasses, the impact of a particular modifier species on the mechanical performance of aluminoborosilicate (ABS) glasses is not well understood. This work compares the indentation properties of six ABS glasses, each of which contains a different network modifier (NWM) with varying field strength (FS). Three alkali and three alkaline earth ABS glasses were designed with low NWM content and [NWM] ≈ [Al₂O₃], to test the modifier FS effect at low concentrations and to maximize three‐coordinated boron. It has been found that both hardness and crack resistance increase with increasing FS in these ABS systems, which is surprising in the context of historical reports. Using¹¹B,²⁷Al, and²⁹Si solid‐state nuclear magnetic resonance, this work provides evidence of how charge distributions differ as a function of NWM species, and how this relates to the observed indentation behaviors.