Single-molecule biophysics articles from across Nature Portfolio

Cryo-electron microscopy (cryo-EM), kinetic analysis and single-molecule biochemistry reveal how the tubulin tyrosine ligase-like 6 (TTLL6) glutamylase binds reads microtubule geometry and modification state of neighboring tubulins, enabling a spatial positive feedback loop for microtubule modification.

Whether bacterial replisome progression follows a “factory” or “track” model remains a long-standing controversy. Here, the authors find that cells can switch between the two models, in a process governed by dynamic chromosome organization processes.

Intraflagellar transport is essential for the formation and function of cilia. Here, the authors use single-molecule imaging in live C. elegans to show that transport trains are formed by the sequential attachment of proteins before departing into the cilium.

We propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5, including a series of structures in lipid nanodiscs, from inactive to fully active, with agonist-bound intermediate states.

Developing disease-modifying drugs for neurodegenerative diseases has been very challenging. Now a machine learning approach has been used to identify small molecule inhibitors of α-synuclein aggregation, a process implicated in Parkinson’s disease and other synucleinopathies. Compounds that bind to the catalytic sites on the surface of the aggregates were identified and then progressively optimized into secondary nucleation inhibitors.

Combining high-speed atomic force microscopy (AFM) with localization AFM and principal component analysis, the authors present six structures of a glutamate transporter and associate the conformational states to the molecule’s activity timeline.

Imaging of fluorescently labelled nascent RNA in live cells enabled real-time observation of transcription of an endogenous gene.

Two studies show that nanopores can identify the 20 proteinogenic amino acids and some of their post-translational modifications. Coupled with an exopeptidase, a bottom-up approach to protein sequencing using nanopores is on the horizon.

Developments in nanopore-based peptide detection and sequencing show promise of a breakthrough.

LIS1 is an essential cofactor for the assembly of the cytoplasmic dynein transport machinery. How LIS1 binding affects dynein motility was unclear. Single-molecule experiments reveal that Pac1 (the yeast homolog of LIS1) binding reduces dynein speed by slowing its detachment from microtubules and does not disrupt the mechanism by which it generates force.

By using fixed charges to engineer a strong electroosmotic flow, we achieve the unidirectional transport of natural polypeptides across nanopores. Our approach enables native proteins to be transported enzymatically and non-enzymatically in the absence of denaturant and electrophoretic tags, with potential applications for protein sequencing.