36 pubs · 1,967 cites · h-index 9
Single-molecule force spectroscopy reveals distinct conformational dynamics induced by SAM versus SAH in SAM-I riboswitches, highlighting divergent RNA stabilization mechanisms.
Riboswitches are structured RNA elements that regulate gene expression upon binding to small molecule ligands. Understanding the mechanisms by which small molecules impact riboswitch activity is key to developing potent, selective ligands for these and other RNA targets. We report the structure-informed design of chemically diverse synthetic ligands for PreQ 1 riboswitches. Multiple X-ray co-crystal structures of synthetic ligands with the Thermoanaerobacter tengcongensis ( Tte )-PreQ 1 riboswitch confirm a common binding site with the cognate ligand, despite considerable chemical differences among the ligands. Structure probing assays demonstrate that one ligand causes conformational changes similar to PreQ 1 in six structurally and mechanistically diverse PreQ 1 riboswitch aptamers. Single-molecule force spectroscopy is used to demonstrate differential modes of riboswitch stabilization by the ligands. Binding of the natural ligand brings about the formation of a persistent, folded pseudoknot structure, whereas a synthetic ligand decreases the rate of unfolding through a kinetic mechanism. Single round transcription termination assays show the biochemical activity of the ligands, while a GFP reporter system reveals compound activity in regulating gene expression in live cells without toxicity. Taken together, this study reveals that diverse small molecules can impact gene expression in live cells by altering conformational changes in RNA structures through distinct mechanisms.
Abstract Riboswitches are structured RNA elements that regulate gene expression upon binding to small molecule ligands. Understanding the mechanisms by which small molecules impact riboswitch activity is key to developing potent, selective ligands for these and other RNA targets. We report the structure-informed design of chemically diverse synthetic ligands for PreQ₁ riboswitches. Multiple X-ray co-crystal structures of synthetic ligands with the Thermoanaerobacter tengcongensis (Tte)-PreQ₁ riboswitch confirm a common binding site with the cognate ligand, despite considerable chemical differences among the ligands. Structure probing assays demonstrate that one ligand causes conformational changes similar to PreQ₁ in six structurally and mechanistically diverse PreQ₁ riboswitch aptamers. Single-molecule force spectroscopy is used to demonstrate differential modes of riboswitch stabilization by the ligands. Binding of the natural ligand brings about the formation of a persistent, folded pseudoknot structure, whereas a synthetic ligand decreases the rate of unfolding through a kinetic mechanism. Single round transcription termination assays show the biochemical activity of the ligands, while a GFP reporter system reveals compound activity in regulating gene expression in live cells without toxicity. Taken together, this study reveals that diverse small molecules can impact gene expression in live cells by altering conformational changes in RNA structures through distinct mechanisms.
Riboswitches are structured RNA elements that regulate gene expression upon binding to small molecule ligands. Understanding the mechanisms by which small molecules impact riboswitch activity is key to developing potent, selective ligands for these and other RNA targets. We report the structure-informed design of chemically diverse synthetic ligands for PreQ
We explore the dynamics of Rydberg excitations in an optical tweezer array under antiblockade (or facilitation) conditions. Because of the finite temperature the atomic positions are randomly spread, an effect that leads to quenched correlated disorder in the interatomic interaction strengths. This drastically affects the facilitation dynamics as we demonstrate experimentally on the elementary example of two atoms. To shed light on the role of disorder in a many-body setting we show that here the dynamics is governed by an Anderson-Fock model, i.e., an Anderson model formulated on a lattice with sites corresponding to many-body Fock states. We first consider a one-dimensional atom chain in a limit that is described by a one-dimensional Anderson-Fock model with disorder on every other site, featuring both localized and delocalized states. We then illustrate the effect of disorder experimentally in a situation in which the system maps on a two-dimensional Anderson-Fock model on a trimmed square lattice. We observe a clear suppression of excitation propagation, which we ascribe to the localization of the many-body wave functions in Hilbert space.
We measure the angular dependence of the resonant dipole-dipole interaction between two individual Rydberg atoms with controlled relative positions. By applying a combination of static electric and magnetic fields on the atoms, we demonstrate the possibility to isolate a single interaction channel at a F\"orster resonance, that shows a well-defined angular dependence. We first identify spectroscopically the F\"orster resonance of choice and we then perform a direct measurement of the interaction strength between the two atoms as a function of the angle between the internuclear axis and the quantization axis. Our results show good agreement with the expected angular dependence ∝(1-3cos²θ), and represent an important step towards quantum state engineering in two-dimensional arrays of individual Rydberg atoms.
We study coherent excitation hopping in a spin chain realized using highly excited individually addressable Rydberg atoms. The dynamics are fully described in terms of an XY spin Hamiltonian with a long range resonant dipole-dipole coupling that scales as the inverse third power of the lattice spacing, C(3)/R(3). The experimental data demonstrate the importance of next neighbor interactions which are manifest as revivals in the excitation dynamics. The results suggest that arrays of Rydberg atoms are ideally suited to large scale, high-fidelity quantum simulation of spin dynamics.
We report on the selective addressing of an individual atom in a pair of single-atom microtraps separated by 30.28em0exμm. Using a tunable light shift, we render the selected atom off-resonant with a global Rydberg excitation laser which is resonant with the other atom, making it possible to selectively block this atom from being excited to the Rydberg state. Furthermore we demonstrate the controlled manipulation of a two-atom entangled state by using the addressing beam to induce a phase shift onto one component of the wave function of the system, transferring it to a dark state for the Rydberg excitation light. Our results are an important step towards implementing quantum information processing and quantum simulation with large arrays of Rydberg atoms.
Holding single ultracold atoms in reconfigurable arrangements makes it possible to study quantum systems. Researchers demonstrate two-dimensional arrays of optical tweezers containing up to 100 traps that can be configured in arbitrary geometries.
We study the Rydberg blockade in a system of three atoms arranged in different two-dimensional geometries (linear and triangular configurations). In the strong blockade regime, we observe high-contrast, coherent collective oscillations of the single excitation probability and an almost perfect van der Waals blockade. Our data are consistent with a total population in doubly and triply excited states below 2%. In the partial blockade regime, we directly observe the anisotropy of the van der Waals interactions between $|nD⟩$ Rydberg states in the triangular configuration. A simple model that only uses independently measured two-body van der Waals interactions fully reproduces the dynamics of the system without any adjustable parameter. These results are extremely promising for scalable quantum information processing and quantum simulation with neutral atoms.