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

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 component...

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Bibliographic Details
Published in:Marine drugs 2022-08, Vol.20 (8), p.503
Main Authors: Paramonov, Alexander S., Shulepko, Mikhail A., Makhonin, Alexey M., Bychkov, Maxim L., Kulbatskii, Dmitrii S., Chernikov, Andrey M., Myshkin, Mikhail Yu, Shabelnikov, Sergey V., Shenkarev, Zakhar O., Kirpichnikov, Mikhail P., Lyukmanova, Ekaterina N.
Format: Article
Language:English
Subjects:
Acetylcholine receptors (nicotinic)
Acetylcholinesterase
Amino acids
Brain
Chemical bonds
Cholinergic transmission
Cholinergics
Coelomic fluids
Coelomocytes
Disulfide bonds
Esterase
Esterases
Gametocytes
Genomes
Hippocampus
Homology
LU-domain
Ly6/uPAR
Lynx2
Lypd6
Mammals
nAChR
Neuromodulation
Neurotransmitters
NMR
Nuclear magnetic resonance
Oocytes
Peptides
Pharmacology
Proteins
Proteomes
three-finger proteins
Toxins
Venom toxins
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Summary: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.
ISSN:1660-3397
1660-3397
DOI:10.3390/md20080503