Author
Sergey A. Goncharuk
Other affiliations: Moscow Institute of Physics and Technology, Moscow State University
Bio: Sergey A. Goncharuk is an academic researcher from Russian Academy of Sciences. The author has contributed to research in topics: Transmembrane domain & Transmembrane protein. The author has an hindex of 9, co-authored 28 publications receiving 303 citations. Previous affiliations of Sergey A. Goncharuk include Moscow Institute of Physics and Technology & Moscow State University.
Papers
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TL;DR: The dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles is described and anFGFR3 signaling mechanism is proposed that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data.
77 citations
TL;DR: It is shown that isotropic bicelles that are applicable for solution NMR spectroscopy behave as predicted by the theoretical models and are likely to be b icelles rather than mixed micelles, if the deuteration of the detergent is not required.
Abstract: Structural studies of membrane proteins are of great importance and interest, with solution and solid state NMR spectroscopy being very promising tools for that task. However, such investigations are hindered by a number of obstacles, and in the first place by the fact that membrane proteins need an adequate environment that models the cell membrane. One of the most widely used and prospective membrane mimetics is isotropic bicelles. While large anisotropic bicelles are well-studied, the field of small bicelles contains a lot of “white spots”. The present work reports the radii of particles and concentration of the detergents in the monomeric state in solutions of isotropic bicelles, formed by 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO), and sodium cholate, as a function of lipid/detergent ratio and temperature. These parameters were measured using 1H NMR d...
42 citations
TL;DR: The proposed technique has three major advantages compared with other existing approaches: it may be used to analyze both weak and relatively strong dimerization/oligomerization processes, it works well for the analysis of complex equilibria, e.g. when monomer, dimer and high-order oligomer populations are simultaneously present in the solution.
36 citations
TL;DR: Structural data provided by NMR provide an insight into the key role of the Cys257 in stabilization of the weak transmembrane dimer in a conformation required for the NGF signaling.
33 citations
TL;DR: The ability of theTLR3 transmembrane domain to form dimers and trimers in detergent micelles was shown by solution NMR spectroscopy and two possible surfaces that may be used for the helix–helix interaction by the full‐length TLR3 were revealed.
32 citations
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TL;DR: This review attempted to combine a comprehensive list of various applications of nanodisc technology with systematic analysis of the most attractive features of this system and advantages provided by nanodISCs for structural and mechanistic studies of membrane proteins.
Abstract: Membrane proteins play a most important part in metabolism, signaling, cell motility, transport, development, and many other biochemical and biophysical processes which constitute fundamentals of life on the molecular level. Detailed understanding of these processes is necessary for the progress of life sciences and biomedical applications. Nanodiscs provide a new and powerful tool for a broad spectrum of biochemical and biophysical studies of membrane proteins and are commonly acknowledged as an optimal membrane mimetic system that provides control over size, composition, and specific functional modifications on the nanometer scale. In this review we attempted to combine a comprehensive list of various applications of nanodisc technology with systematic analysis of the most attractive features of this system and advantages provided by nanodiscs for structural and mechanistic studies of membrane proteins.
365 citations
TL;DR: Nanodisc technology provides important advantages for the isolation, purification, structural resolution and functional characterization of membrane proteins, and the ability to precisely control the nanodisc composition provides a nanoscale membrane surface for investigating molecular recognition events.
Abstract: Membrane proteins have long presented a challenge to biochemical and functional studies. In the absence of a bilayer environment, individual proteins and critical macromolecular complexes may be insoluble and may display altered or absent activities. Nanodisc technology provides important advantages for the isolation, purification, structural resolution and functional characterization of membrane proteins. In addition, the ability to precisely control the nanodisc composition provides a nanoscale membrane surface for investigating molecular recognition events.
336 citations
TL;DR: This study establishes the existence of multiple active ligand-bound states, and uncovers a novel molecular mechanism through which FGFR-linked pathologies can arise.
Abstract: Fibroblast growth factors (fgfs) are widely believed to activate their receptors by mediating receptor dimerization. Here we show, however, that the FGF receptors form dimers in the absence of ligand, and that these unliganded dimers are phosphorylated. We further show that ligand binding triggers structural changes in the FGFR dimers, which increase FGFR phosphorylation. The observed effects due to the ligands fgf1 and fgf2 are very different. The fgf2-bound dimer structure ensures the smallest separation between the transmembrane (TM) domains and the highest possible phosphorylation, a conclusion that is supported by a strong correlation between TM helix separation in the dimer and kinase phosphorylation. The pathogenic A391E mutation in FGFR3 TM domain emulates the action of fgf2, trapping the FGFR3 dimer in its most active state. This study establishes the existence of multiple active ligand-bound states, and uncovers a novel molecular mechanism through which FGFR-linked pathologies can arise.
193 citations
TL;DR: Current understanding in the field of transmembrane helix dimerization is reviewed, as it has evolved from the paradigm of sequence motifs into a view in which the interactions between TM helices are much more complex.
159 citations
TL;DR: Recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins agree well with those identified by complementary experimental techniques, demonstrating the power of the molecular dynamics approach in the prediction and characterization of lipid interaction Sites on integral membrane proteins.
147 citations