Manipulation of Time- and Frequency-Domain Dynamics by Magnon-Magnon Coupling in Synthetic Antiferromagnets

Magnons (the quanta of spin waves) could be used to encode information in beyond Moore computing applications. In this study, the magnon coupling between acoustic mode and optic mode in synthetic antiferromagnets (SAFs) is investigated by micromagnetic simulations. For a symmetrical SAF system, the time-evolution magnetizations of the two ferromagnetic layers oscillate in-phase at the acoustic mode and out-of-phase at the optic mode, showing an obvious crossing point in their antiferromagnetic resonance spectra. However, the symmetry breaking in an asymmetrical SAF system by the thickness difference, can induce an anti-crossing gap between the two frequency branches of resonance modes and thereby a strong magnon-magnon coupling appears between the resonance modes. The magnon coupling induced a hybridized resonance mode and its phase difference varies with the coupling strength. The maximum coupling occurs at the bias magnetic field at which the two ferromagnetic layers oscillate with a 90° phase difference. Besides, we show how the resonance modes in SAFs change from the in-phase state to the out-of-phase state by slightly tuning the magnon-magnon coupling strength. Our work provides a clear physical picture for the understanding of magnon-magnon coupling in a SAF system and may provide an opportunity to handle the magnon interaction in synthetic antiferromagnetic spintronics.

Global Dynamics as Communication Sensors in Peptide Synthetase Cyclization Domains.

Structural biology is the foundation for deriving molecular mechanisms, where snapshots of macromolecules and binding partners inform on mutations that test or modify function. However, frequently, the impact of mutations violates the underpinnings of structural models, and mechanisms become cryptic. This conundrum applies to multidomain enzymatic systems called nonribosomal peptide synthetases (NRPSs), which assemble simple substrates into complex metabolites often with pharmaceutical properties. Engineering NRPSs can generate new pharmaceuticals, but a dynamic domain organization challenges rational design. Using nuclear magnetic resonance (NMR), we determined the solution structure of a 52 kDa cyclization domain and demonstrate that global intra-domain dynamics enable sensing of substrates tethered to partner domains and draw an allosteric response encompassing the enzyme′s buried active site and two binding sites 40 Å apart. We show that a point-site mutation that impedes the domain dynamics globally hampers the allosteric response. We demonstrate this mechanism through NMR experiments that provide atomic-level read-outs of allosteric responses during biochemical transformations in situ. Our results establish global structural dynamics as sensors of molecular events that can remodel domain interactions and illustrate the need for integrating structural dynamics explicitly when deriving molecular mechanisms through mutagenesis and structural biology.

Remodeling of Conformational Dynamics Enhances Catalytic Activities of M1 Zinc-metallopeptidases from Lanthipeptide Biosynthesis

Lanthipeptides are an important group of natural products with diverse biological functions, and their biosynthesis requires the removal of N-terminal leader peptides (LPs) by designated proteases. LanPM1 enzymes, a subgroup of M1 zinc-metallopeptidases, are recently identified as bifunctional proteases with both endo- and aminopeptidase activities to remove LPs of class III and class IV lanthipeptides. Herein, we report the biochemical and structural characterization of EryP as the LanPM1 enzyme from the biosynthesis of class III lanthipeptide erythreapeptin. We determined X-ray crystal structures of EryP in three conformational states, the open, intermediate and closed states and identified a unique inter-domain Ca binding site as a regulatory element to modulate its domain dynamics and proteolytic activity. Inspired by the regulatory Ca binding, we develop a strategy to engineer LanPM1 enzymes for enhanced catalytic activities by strengthening inter-domain associations and driving the conformational equilibrium toward their closed forms.

UbiD domain dynamics underpins aromatic decarboxylation

The widespread UbiD enzyme family utilises the prFMN cofactor to achieve reversible decarboxylation of acrylic and (hetero)aromatic compounds. The reaction with acrylic compounds based on reversible 1,3-dipolar cycloaddition between substrate and prFMN occurs within the confines of the active site. In contrast, during aromatic acid decarboxylation, substantial rearrangement of the substrate aromatic moiety associated with covalent catalysis presents a molecular dynamic challenge. Here we determine the crystal structures of the multi-subunit vanillic acid decarboxylase VdcCD. We demonstrate that the small VdcD subunit acts as an allosteric activator of the UbiD-like VdcC. Comparison of distinct VdcCD structures reveals domain motion of the prFMN-binding domain directly affects active site architecture. Docking of substrate and prFMN-adduct species reveals active site reorganisation coupled to domain motion supports rearrangement of the substrate aromatic moiety. Together with kinetic solvent viscosity effects, this establishes prFMN covalent catalysis of aromatic (de)carboxylation is afforded by UbiD dynamics.