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Conus ventricosus

ABSTRACT: Lautoconus ventricosus genome sequencing and assembly

PROVIDER: PRJNA678883 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR13757741_1.fastq.gz	Fastqsanger.gz
	SRR13757741_2.fastq.gz	Fastqsanger.gz
	SRR13740844_1.fastq.gz	Fastqsanger.gz
	SRR13740844_2.fastq.gz	Fastqsanger.gz

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Project description:?6-containing (?6*) nicotinic acetylcholine receptors (nAChRs) are expressed throughout the periphery and the central nervous system and constitute putative therapeutic targets in pain, addiction and movement disorders. The ?6?2* nAChRs are relatively well studied, in part due to the availability of target specific ?-conotoxins (?-Ctxs). In contrast, all native ?-Ctxs identified that potently block ?6?4 nAChRs exhibit higher potencies for the closely related ?6?2?3 and/or ?3?4 subtypes. In this study, we have identified a novel peptide from Conus ventricosus with pronounced selectivity for the ?6?4 nAChR. The peptide-encoding gene was cloned from genomic DNA and the predicted mature peptide, ?-Ctx VnIB, was synthesized. The functional properties of VnIB were characterized at rat and human nAChRs expressed in Xenopus oocytes by two-electrode voltage clamp electrophysiology. VnIB potently inhibited ACh-evoked currents at r?6?4 and r?6/?3?4 nAChRs, displayed ?20-fold and ?250-fold lower potencies at r?3?4 and r?6/?3?2?3 receptors, respectively, and exhibited negligible effects at eight other nAChR subtypes. Interestingly, even higher degrees of selectivity were observed for h?6/?3?4 over h?6/?3?2?3 and h?3?4 receptors. Finally, VnIB displayed fast binding kinetics at r?6/?3?4 (on-rate t½?=?0.87 min-1, off-rate t½?=?2.7 min-1). The overall preference of VnIB for ?4* over ?2* nAChRs is similar to the selectivity profiles of other 4/6 ?-Ctxs. However, in contrast to previously identified native ?-Ctxs targeting ?6* nAChRs, VnIB displays pronounced selectivity for ?6?4 nAChRs over both ?3?4 and ?6?2?3 receptors. VnIB thus represents a novel molecular probe for elucidating the physiological role and therapeutic properties of ?6?4* nAChRs.

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