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Biology subjects

Terry, D. S.

Publications and source records attributed to Terry, D. S..

3 recordsLinked to original sources

EMhub: a web platform for data management and on-the-fly processing in scientific facilities

Most scientific facilities produce large amounts of heterogeneous data at a rapid pace. Managing users, instruments, reports, and invoices presents additional challenges. To address these challenges, we introduce EMhub, a web platform designed to support the daily operations and record-keeping of a scientific facility. EMhub enables easy management of user information, instruments, bookings, and projects. The application was initially developed to meet the needs of a CryoEM facility, but its functionality and adaptability have proven broad enough to be extended to other data-generating centers. The expansion of EMHub is enabled by the modular nature of its core functionalities. The application allows external processes to be connected via a REST API, automating tasks such as folder creation, user and password generation, and execution of real-time data processing pipelines. EMhub has been used for several years at the Swedish National CryoEM Facility and installed in the CryoEM center at the Structural Biology Department at St. Jude Childrens Research Hospital. A fully automated single-particle pipeline has been implemented for on-the-fly data processing and analysis. At St. Jude, the X-Ray Crystallography Center and the Single-Molecule Imaging Center have already expanded the platform to support their operational and data management workflows.

biophysics↗

Real-time conformational dynamics of SARS-CoV-2 spikes on virus particles

SARS-CoV-2 spike (S) mediates entry into cells and is critical for vaccine development against COVID-19. Structural studies have revealed distinct conformations of S, but real-time information that connects these structures, is lacking. Here we apply single-molecule Forster Resonance Energy Transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to hACE2, S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences of convalescent plasma and antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to RBD or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design.

microbiology↗

The allosteric mechanism of substrate-specific transport in SLC6 is mediated by a volumetric sensor

Neurotransmitter:sodium symporters (NSS) in the SLC6 family terminate neurotransmission by coupling the thermodynamically favorable transport of ions to the thermodynamically unfavorable transport of neurotransmitter back into presynaptic neurons. While a combination of structural, functional, and computational studies on LeuT, a bacterial NSS homolog, has provided critical insight into the mechanism of sodium-coupled transport, the mechanism underlying substrate-specific transport rates is still not understood. We present a combination of MD simulations, single-molecule FRET imaging, and measurements of Na+ binding and substrate transport that reveal an allosteric mechanism in which residues F259 and I359 in the substrate binding pocket couple substrate binding to Na+ release from the Na2 site through allosteric modulation of the stability of a partially-open, inward-facing state. We propose a new model for transport selectivity in which the two residues act as a volumetric sensor that inhibits the transport of bulky amino acids.

biophysics↗