Single-molecule studies reveal the off-pathway early paused state intermediates as a target of streptolydigin inhibition of RNA polymerase and its dramatic enhancement by Gre factors.

Antibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes (ECs) of RNAP in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected.

On the Properties of Styrene-Maleic Acid Copolymer-Lipid Nanoparticles: A Solution NMR Perspective.

The production of functionally active membrane proteins (MPs) in an adequate membrane environment is a key step in structural biology. Polymer-lipid particles based on styrene and maleic acid (SMA) represent a promising type of membrane mimic, as they can extract properly folded MPs directly from their native lipid environment. However, the original SMA polymer is sensitive to acidic pH levels, which has led to the development of several modifications: SMA-EA, SMA-QA, and others.

Structural basis for the transmembrane signaling and antidepressant-induced activation of the receptor tyrosine kinase TrkB.

Neurotrophin receptors of the Trk family are involved in the regulation of brain development and neuroplasticity, and therefore can serve as targets for anti-cancer and stroke-recovery drugs, antidepressants, and many others. The structures of Trk protein domains in various states upon activation need to be elucidated to allow rational drug design. However, little is known about the conformations of the transmembrane and juxtamembrane domains of Trk receptors.

TIR domains of TLR family-from the cell culture to the protein sample for structural studies.

Toll-like receptors (TLRs) are key players in the innate immune system. Despite the great efforts in TLR structural biology, today we know the spatial structures of only four human TLR intracellular TIR domains. All of them belong to one of five subfamilies of receptors.