Ekaterina Lyukmanova

Ekaterina Lukmanova's laboratory investigates human three-loop proteins of the Ly6/uPAR family and related neurotoxins from snake venom. The focus is on the molecular mechanisms of interaction of the studied proteins with their receptors. The laboratory team owns advanced technologies for the recombinant production of "three-loop" proteins that are not available from natural sources. This allowed for the first time to study the spatial structure and conduct a number of functional studies of such human proteins as Lynx1 and Lypd6 (neuroplasticity regulation factors), as well as SLURP-1 and SLURP-2 (auto/paracrine regulators of epithelial cells). Based on these proteins, the development of prototype drugs that improve cognitive function, anti-cancer drugs, as well as drugs aimed at the treatment of a number of skin diseases is currently being developed.
Laboratory research is carried out using the methods of protein engineering, cell biology, neurophysiology, electrophysiology and structural biology. In the field of NMR spectroscopy, the laboratory cooperates with the Laboratory of Structural Biology of Ion Channels of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, in the study of voltage-gated human ion channels. Recently, the laboratory has been actively developing structural studies of ion channels using cryo-electron microscopy. The combined use of NMR spectroscopy, cryoelectron microscopy, and computer simulation made it possible for the first time to reveal an unusual type of interaction between a three-loop neurotoxin and the nicotinic acetylcholine receptor.

1. Shulepko MA, Bychkov ML, Shenkarev ZO, Kulbatskii DS, Makhonin AM, Paramonov AS, Chugunov AO, Kirpichnikov MP, Lyukmanova EN. Biochemical Basis of Skin Disease Mal de Meleda: SLURP-1 Mutants Differently Affect Keratinocyte Proliferation and Apoptosis. J Invest Dermatol. 2021 Sep;141(9):2229-2237. doi: 10.1016/j.jid.2021.01.035. Epub 2021 Mar 16. PMID: 33741389.

2. Shenkarev ZO, Shulepko MA, Bychkov ML, Kulbatskii DS, Shlepova OV, Vasilyeva NA, Andreev-Andrievskiy AA, Popova AS, Lagereva EA, Loktyushov EV, Koshelev SG, Thomsen MS, Dolgikh DA, Kozlov SA, Balaban PM, Kirpichnikov MP, Lyukmanova EN. Water-soluble variant of human Lynx1 positively modulates synaptic plasticity and ameliorates cognitive impairment associated with α7-nAChR dysfunction. J Neurochem. 2020 Oct;155(1):45-61. doi: 10.1111/jnc.15018. Epub 2020 May 10. PMID: 32222974.

3. Bychkov M, Shulepko M, Osmakov D, Andreev Y, Sudarikova A, Vasileva V, Pavlyukov MS, Latyshev YA, Potapov AA, Kirpichnikov M, Shenkarev ZO, Lyukmanova E. Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a. Cancers (Basel). 2020 Jul 8;12(7):1837. doi: 10.3390/cancers12071837. PMID: 32650495; PMCID: PMC7408772.

4. Lyukmanova EN, Bychkov ML, Sharonov GV, Efremenko AV, Shulepko MA, Kulbatskii DS, Shenkarev ZO, Feofanov AV, Dolgikh DA, Kirpichnikov MP. Human secreted proteins SLURP-1 and SLURP-2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors. Br J Pharmacol. 2018 Jun;175(11):1973-1986. doi: 10.1111/bph.14194. Epub 2018 Apr 24. PMID: 29505672; PMCID: PMC5980222.

5. Männikkö R, Shenkarev ZO, Thor MG, Berkut AA, Myshkin MY, Paramonov AS, Kulbatskii DS, Kuzmin DA, Sampedro Castañeda M, King L, Wilson ER, Lyukmanova EN, Kirpichnikov MP, Schorge S, Bosmans F, Hanna MG, Kullmann DM, Vassilevski AA. Spider toxin inhibits gating pore currents underlying periodic paralysis. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4495-4500. doi: 10.1073/pnas.1720185115. Epub 2018 Apr 10. PMID: 29636418; PMCID: PMC5924911.

6. Thomsen MS, Arvaniti M, Jensen MM, Shulepko MA, Dolgikh DA, Pinborg LH, Härtig W, Lyukmanova EN, Mikkelsen JD. Lynx1 and Aβ1-42 bind competitively to multiple nicotinic acetylcholine receptor subtypes. Neurobiol Aging. 2016 Oct;46:13-21. doi: 10.1016/j.neurobiolaging.2016.06.009. Epub 2016 Jun 17. PMID: 27460145.

7. Lyukmanova EN, Shenkarev ZO, Paramonov AS, Sobol AG, Ovchinnikova TV, Chupin VV, Kirpichnikov MP, Blommers MJ, Arseniev AS. Lipid-protein nanoscale bilayers: a versatile medium for NMR investigations of membrane proteins and membrane-active peptides. J Am Chem Soc. 2008 Feb 20;130(7):2140-1. doi: 10.1021/ja0777988. Epub 2008 Jan 30. PMID: 18229924.