PeriodCountry, cityEducation institutionAdditional info
2005–2011 Russia, Dolgoprudny Moscow institute of physics and technology

Selected publications

  1. Bocharov E.V., Mineev K.S., Pavlov K.V., Akimov S.A., Kuznetsov A.S., Efremov R.G., Arseniev A.S. (2016). Helix-helix interactions in membrane domains of bitopic proteins: Specificity and role of lipid environment. Biochim. Biophys. Acta , [+]

    Interaction between transmembrane helices often determines biological activity of membrane proteins. Bitopic proteins, a broad subclass of membrane proteins, form dimers containing two membrane-spanning helices. Some aspects of their structure-function relationship cannot be fully understood without considering the protein-lipid interaction, which can determine the protein conformational ensemble. Experimental and computer modeling data concerning transmembrane parts of bitopic proteins are reviewed in the present paper. They highlight the importance of lipid-protein interactions and resolve certain paradoxes in the behavior of such proteins. Besides, some properties of membrane organization provided a clue to understanding of allosteric interactions between distant parts of proteins. Interactions of these kinds appear to underlie a signaling mechanism, which could be widely employed in the functioning of many membrane proteins. Treatment of membrane proteins as parts of integrated fine-tuned proteolipid system promises new insights into biological function mechanisms and approaches to drug design.

  2. Кузнецов А.С., Ефремов Р.Г. (2016). Оценка влияния среды на димеризацию трансмембранных доменов гликофорина А в компьютерном эксперименте. Актуальные вопросы биологической физики и химии 1 (1), 250–254 [+]

    Here we present a combined method to study mutual effects of a protein and a membrane upon the dimerization of transmembrane (TM) α-helical peptides. The approach was tested on the TM domains of human glycophorin A (GpA) and several model peptides. It is shown that lipids contribute significantly to a total free energy of dimerization, and the direct protein-protein contacts may be unfavorable. Also, we found some lipid acyl chains binding sides on the surface of TM domains of GpA. Thus, the amino acid sequence determines not only the protein- protein contacts during dimerization, but also the interactions with lipids, and that can determine the detailed balance between the free energy contributions.

  3. Maurice P., Baud S., Bocharova O.V., Bocharov E.V., Kuznetsov A.S., Kawecki C., Bocquet O., RomierCrouzet B., Gorisse L., Ghirardi M., Duca L., Blaise S., Martiny L., Dauchez M., Efremov R.G., Debelle L. (2016). New insights into molecular organization of human neuraminidase-1: transmembrane topology and dimerization ability. Sci Rep 6, 38363 [+]

    Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139–159 (TM1) and 316–333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.

  4. Kuznetsov A.S., Polyansky A.A., Fleck M., Volynsky P.E., Efremov R.G. (2015). Adaptable Lipid Matrix Promotes Protein-Protein Association in Membranes. J. Chem. Theory Comput. 11 (9), 4415–26 [+]

    Transmembrane domains play an important role in the functioning of membrane proteins. Their interactions determine the operation of many receptors, in particular, receptor tyrosine kinases. In current work it was shown for glycophorin A and two model peptides that the lipid bilayer plays a major role in the dimerization of transmembrane helices. Peptide incorporation into the membrane cause the formation of specific heterogeneities. Thus, the dimerization of transmembrane helices may have an entropic nature.

  5. Kuznetsov A.S., Volynsky P.E., Efremov R.G. (2015). Role of the Lipid Environment in the Dimerization of Transmembrane Domains of Glycophorin A. Acta Naturae 7 (4), 122–7 [+]

    An efficient computational approach is developed to quantify the free energy of a spontaneous association of the α-helices of proteins in the membrane environment. The approach is based on the numerical decomposition of the free energy profiles of the transmembrane (TM) helices into components corresponding to protein-protein, protein-lipid, and protein-water interactions. The method was tested for the TM segments of human glycophorin A (GpA) and two mutant forms, Gly83Ala and Thr87Val. It was shown that lipids make a significant negative contribution to the free energy of dimerization, while amino acid residues forming the interface of the helix-helix contact may be unfavorable in terms of free energy. The detailed balance between different energy contributions is highly dependent on the amino acid sequence of the TM protein segment. The results show the dominant role of the environment in the interaction of membrane proteins that is changing our notion of the driving force behind the spontaneous association of TM α-helices. Adequate estimation of the contribution of the water-lipid environment thus becomes an extremely urgent task for a rational design of new molecules targeting bitopic membrane proteins, including receptor tyrosine kinases.

  6. Кузнецов А.С., Дубовский П.В., Воронцова О.В., Феофанов А.В., Ефремов Р.Г. (2014). Взаимодействие линейных катионных пептидов с фосфолипидными мембранами и полимерами сиаловой кислоты. Биохимия 79 (5), 583–594583–594 ID:1123