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Receptor Interacting Protein Kinase 3 (RIPK3) has a key role in TNF-induced necroptosis. Here, the authors combine solid state NMR measurements, MD simulations and cell based assays to characterize mouse RIPK3 and they present the structure of the RIPK3 amyloid core.

Structures of antifungal AmB ‘sponges’ are illuminated by high-resolution SSNMR. These AmB assemblies consist of asymmetric head-to-tail homodimers staggered in a clathrate-like lattice with large void volumes similar to the size of sterols.

HORNET, a method that uses unsupervised machine learning and deep neural networks to analyse atomic force microscopy data enables structural determination of RNA molecules in multiple conformations.

Here, the authors identify a small molecule degrader (XL44) for hRpn13 and solve the XL44-hRpn13 structure. XL44 induces apoptosis in myeloma cells with hRpn13 dependency and also targets KEN box proteins PCLAF and RRM2. Loss of hRpn13 and PCLAF abrogates XL44 restriction of cell viability.

A study reports the development of a structural derivative of amphotericin B with broad antifungal activity in mice but without the renal toxicity associated with amphotericin B.

The accumulation of alpha-synuclein fibrils within neurons is the defining feature of Lewy body dementia (LBD). Here the authors report a method to produce large quantities of alpha-synuclein fibrils that reproduce the complex structure of the fibrils that accumulate in LBD brain tissue.

RNA conformational heterogeneity is important to diverse functions. Here, the authors use AFM to directly visualize individual RNA molecules that are in various conformational states under near physiological solution conditions for the first time.

α-synuclein amyloid fibrils are associated with Parkinson's disease. SSNMR analyses now reveal the atomic structure of a pathogenic human α-synuclein fibril, providing a framework for understanding fibril nucleation, propagation and interactions with small molecules.

Rpn13 is a substrate receptor of the 26S proteasome and an anti-cancer drug target. Here, the authors identify and characterize XL5, a lead compound that binds to the N-terminal Pru domain of human Rpn13 (hRpn13), solve the NMR structure of XL5-ligated hRpn13 Pru and develop XL5-PROTACs that preferentially target an identified hRpn13 Pru fragment present in multiple myeloma cells.

Enzyme I (EI)—a component of the bacterial phosphotransferase signal transduction system—undergoes large conformational rearrangements upon substrate binding. Here the authors show that the EI open-to-closed conformational switch occurs through suppression of micro- to millisecond dynamics of C-terminal domain.

Structures of HIV-1 capsid protein (CA) in tubular assemblies, determined by MAS-NMR, reveal the basis of CA’s conformational plasticity.

NMR structure determination is challenging for proteins with a molecular weight above 30 kDa and atomic-resolution structure determination from cryo-EM data is currently not the rule. Here the authors describe an integrated structure determination approach that simultaneously uses NMR and EM data and allows them to determine the structure of the 468 kDa dodecameric aminopeptidase TET2 complex.

Despite recent progress, solving protein structures using solid-state NMR spectroscopy is not routine. Now, a method for the rapid determination of global protein fold is reported, based on measurements of ¹⁵N longitudinal paramagnetic relaxation enhancements in several protein variants modified with covalently attached cysteine–EDTA–Cu²⁺ tags.

NMR structures of the homodimeric repressor protein CylR2 collected from 25 °C to –16 °C provide glimpses of the molecular changes that occur during cold denaturation, yielding insights into protein folding and oligomerization.

It is well known that large-scale rearrangements of domains of a protein can play an important role in ligand binding and recognition, catalysis, and regulation. Though X-ray crystal structures can provide a static picture of the apo (usually open) and holo (usually closed) states of a protein, it is not usually clear whether the apo state exists as a single species where the closed state is energetically inaccessible and interdomain rearrangement is induced by ligand or substrate binding or whether the predominantly open form already co-exists in rapid equilibrium with a minor closed species. In this paper, the authors obtained paramagnetic relaxation enhancement data that indicate that there is a rapidly exchanging mixture of a predominantly open form of the maltose-binding protein and a minor (partially-closed) form of the protein. Ensemble simulated annealing refinement was used to determine an ensemble average structure of the minor apo species and demonstrate that it is distinct from the sugar-bound state.

A structural study of the CD28 hinge used in CAR T-cells reveals local structural elements amidst intrinsic disorder that may affect the spacing between the antigen recognition and transmembrane domains to impact CAR T-cell recognition and signaling.

Structural analysis reveals an intermediate (excited) state of GMPPNP-bound KRAS^G13D which includes the formation of a new pocket in the allosteric lobe that could be exploited for developing new therapeutics against KRAS^G13D-driven cancers.