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

Title: New Three-Finger Protein from Starfish Asteria rubens Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2
Authors: Alexander S. Paramonov; 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; Ekaterina N. Lyukmanova
Source: Marine Drugs, Vol 20, Iss 8, p 503 (2022)
Publisher Information: MDPI AG
Publication Year: 2022
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Ly6/uPAR; three-finger proteins; LU-domain; nAChR; Lynx2; Lypd6; Biology (General); QH301-705.5
Description: 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.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.mdpi.com/1660-3397/20/8/503; https://doaj.org/toc/1660-3397; https://doaj.org/article/c9dc58cc334d4852948d18e54962e1f7
DOI: 10.3390/md20080503
Availability: https://doi.org/10.3390/md20080503; https://doaj.org/article/c9dc58cc334d4852948d18e54962e1f7
Accession Number: edsbas.BEAF884C
Database: BASE