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Volume 20
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10.3390/md20080503
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Article

New Three-Finger Protein from Starfish Asteria rubens Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2

by
Alexander S. Paramonov
1,
Mikhail A. Shulepko
1,
Alexey M. Makhonin
1,2,
Maxim L. Bychkov
1,
Dmitrii S. Kulbatskii
1,
Andrey M. Chernikov
1,3,
Mikhail Yu. Myshkin
1,
Sergey V. Shabelnikov
4,
Zakhar O. Shenkarev
1,5,
Mikhail P. Kirpichnikov
1,3 and
Ekaterina N. Lyukmanova
1,3,5,*
1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str. 16/10, 119997 Moscow, Russia
2
AI Centre, National Research University Higher School of Economics, Myasnitskaya Str. 20, 101000 Moscow, Russia
3
Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of the Living Systems and Synthetic Biology”, Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, 119234 Moscow, Russia
4
Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Prospect 4, 194064 St. Petersburg, Russia
5
Moscow Institute of Physics and Technology, State University, Institutskiy Per. 9, 141701 Moscow, Russia
*
Author to whom correspondence should be addressed.
Mar. Drugs 2022, 20(8), 503; https://doi.org/10.3390/md20080503
Submission received: 8 July 2022 / Revised: 27 July 2022 / Accepted: 29 July 2022 / Published: 3 August 2022
(This article belongs to the Section Marine Pharmacology)
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Abstract

Three-finger proteins (TFPs) are small proteins with characteristic three-finger β-structural fold stabilized by the system of conserved disulfide bonds. These proteins have been found in organisms from different taxonomic groups and perform various important regulatory functions or act as components of snake venoms. Recently, four TFPs (Lystars 1–4) with unknown function were identified in the coelomic fluid proteome of starfish A. rubens. Here we analyzed the genomes of A. rubens and A. planci starfishes and predicted additional five and six proteins containing three-finger domains, respectively. One of them, named Lystar5, is expressed in A. rubens coelomocytes and has sequence homology to the human brain neuromodulator Lynx2. The three-finger structure of Lystar5 close to the structure of Lynx2 was confirmed by NMR. Similar to Lynx2, Lystar5 negatively modulated α4β2 nicotinic acetylcholine receptors (nAChRs) expressed in X. laevis oocytes. Incubation with Lystar5 decreased the expression of acetylcholine esterase and α4 and α7 nAChR subunits in the hippocampal neurons. In summary, for the first time we reported modulator of the cholinergic system in starfish.
Keywords: Ly6/uPAR; three-finger proteins; LU-domain; nAChR; Lynx2; Lypd6; Lynx1; Lypd6b Ly6/uPAR; three-finger proteins; LU-domain; nAChR; Lynx2; Lypd6; Lynx1; Lypd6b

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MDPI and ACS Style

Paramonov, A.S.; Shulepko, M.A.; Makhonin, A.M.; Bychkov, M.L.; Kulbatskii, D.S.; Chernikov, A.M.; Myshkin, M.Y.; Shabelnikov, S.V.; Shenkarev, Z.O.; Kirpichnikov, M.P.; et al. New Three-Finger Protein from Starfish Asteria rubens Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2. Mar. Drugs 2022, 20, 503. https://doi.org/10.3390/md20080503

AMA Style

Paramonov AS, Shulepko MA, Makhonin AM, Bychkov ML, Kulbatskii DS, Chernikov AM, Myshkin MY, Shabelnikov SV, Shenkarev ZO, Kirpichnikov MP, et al. New Three-Finger Protein from Starfish Asteria rubens Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2. Marine Drugs. 2022; 20(8):503. https://doi.org/10.3390/md20080503

Chicago/Turabian Style

Paramonov, Alexander S., Mikhail A. Shulepko, Alexey M. Makhonin, Maxim L. Bychkov, Dmitrii S. Kulbatskii, Andrey M. Chernikov, Mikhail Yu. Myshkin, Sergey V. Shabelnikov, Zakhar O. Shenkarev, Mikhail P. Kirpichnikov, and et al. 2022. "New Three-Finger Protein from Starfish Asteria rubens Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2" Marine Drugs 20, no. 8: 503. https://doi.org/10.3390/md20080503

APA Style

Paramonov, A. S., Shulepko, M. A., Makhonin, A. M., Bychkov, M. L., Kulbatskii, D. S., Chernikov, A. M., Myshkin, M. Y., Shabelnikov, S. V., Shenkarev, Z. O., Kirpichnikov, M. P., & Lyukmanova, E. N. (2022). New Three-Finger Protein from Starfish Asteria rubens Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2. Marine Drugs, 20(8), 503. https://doi.org/10.3390/md20080503

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