Press-room / Digest
Mechanism of coelenterazine chromophore photoinactivation from Beroe abissycola photoprotein is proposed
Scientists from IBCh RAS with colleagues from Photobiology Lab (IBP SB RAS) elucidated the structures of Beroe abissycola photoprotein’s chromophore photoinactivation products and proposed a mechanism of the photoinactivation process. The similarity of chemical transformations of photoprotein and GFP-like fluorescent protein chromophores was demonstrated for the first time. The results are published in Organic Letters. The project was funded by the RScF grant № 17-14-01169p. Learn more
Spotlight on the protein corona of liposomes
Liposomes are an established drug delivery platform that has paved the way to clinic for nanomedicine drugs. In the body, interactions of liposomes, as well as other drug delivery vehicles, are mediated by the complex dynamic layer of plasma proteins adsorbed on the surface, the protein corona. The review summarizes the data on liposome protein corona, tracing the path from interactions of individual proteins to the effects mediated by the corona in vivo. It critically assesses protein corona isolation and analysis techniques and offers a classification of the approaches to exploitation of the protein corona—rather than elimination thereof—based on the bilayer composition–protein corona composition–molecular interactions–biological performance relationship.
Essential role of zinc ions in TLR1 receptor activation
Toll-like receptors are the key players of the innate immune response. Despite the numerous studies and huge amount of data regarding these proteins, the structural basis of their functioning has not yet been clearly elucidated. Scientists from IBCh RAS, together with their colleagues from Moscow Institute of Physics and Technology and Changchun Institute of Applied Chemistry (China) discovered the essential role of zinc in the functioning of Toll-like receptor 1 and proposed possible mechanisms of zinc-mediated receptor activation. The work was funded by the RFBR grant 20-34-70024 and published in Communications Biology.
New structural data allowed to study the mechanism of thermal activation of thermosensitive ion channels of the TRP family
Scientists from the Laboratory of biomolecular modeling of the IBCh RAS, together with colleagues from USA and Czech Republic, have revealed the structural mechanism of heat-induced opening of temperature-sensitive TRP channels. TRPV3 is a polymodal receptor that works as a temperature sensor in skin keratinocytes. For the first time, the team of scientists succeeded in capturing the protein in a closed, sensitized (intermediate), and open state using Cryo-EM. Based on the structural data, the authors proposed the molecular mechanism for the thermal activation of the channel, which represented the so-called "conformational wave" of rearrangements within the protein and its lipid environment. This work was published in the prestigious journal Nature Structural & Molecular Biology and was awarded a cover of the issue. Learn more
Unambiguous Tracking of Protein Phosphorylation by Fast High-Resolution FOSY NMR
Dysregulation of post-translational modifications (PTMs) like phosphorylation is often involved in disease. NMR may elucidate exact loci and time courses of PTMs at atomic resolution and near-physiological conditions but requires signal assignment to individual atoms. Conventional NMR methods for this base on tedious global signal assignment that may often fail, as for large intrinsically disordered proteins (IDPs). We present a sensitive, robust alternative to rapidly obtain only the local assignment near affected signals, based on FOcused SpectroscopY (FOSY) experiments using selective polarisation transfer (SPT). We prove its efficiency by identifying two phosphorylation sites of glycogen synthase kinase 3 beta (GSK3β) in human Tau40, an IDP of 441 residues, where the extreme spectral dispersion in FOSY revealed unprimed phosphorylation also of Ser409. FOSY may broadly benefit NMR studies of PTMs and other hotspots in IDPs, including sites involved in molecular interactions.