A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar melanocortin 1 receptor agonist
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Authors: Ericson, Mark D.; Schnell, Sathya M.; Freeman, Katie T.; Haskell-Luevano, Carrie
Abstract
The melanocortin system consists of five receptor subtypes (MC1-5R), endogenous agonists derived from the proopiomelanocortin gene transcript, and the antagonists agouti and agouti-related protein. The Escherichia coli heat shock protein ClpB has previously been described as an antigen mimetic to the endogenous melanocortin agonist alpha-MSH. Herein, we investigated if a fragment of the ClpB protein could directly signal through the melanocortin receptors. We synthesized a complementary fragment of the ClpB protein that partially aligned with alpha-MSH. Pharmacological assessment of this fragment resulted in no antagonist activity at the MC3R or the MC4R and no agonist activity at the MC4R. Partial receptor activation was observed for the MC3R and MC5R at 100 mu M concentrations. This fragment was shown to be a full micromolar MC1R agonist and may serve as a template for future research into selective MC1R ligands. (C) 2015 Elsevier Ltd. All rights reserved.
Molecular cloning and expression analysis of mc5r like genes (mc5rl) in Ruditapes philippinarum (Manila clam) after aerial exposure and low-temperature stress
MOLECULAR BIOLOGY REPORTS
Authors: Jiang, Kunyin; Nie, Hongtao; Yan, Xiwu
Abstract
The melanocortin-5 receptor (mc5r) plays an important role in exocrine function, lipid metabolism, obesity, and stress response in the vertebrate. However, the functions of the mc5r in mollusks have been rarely investigated. We cloned the full length of Ruditapes philippinarum mc5r like gene (mc5rl) and the sequence structure and phylogenetic relationship of mc5rl were analyzed. Besides, we detected the tissue distribution and the expression pattern of R. philippinarum mc5r like (mc5rl) genes after aerial exposure and low-temperature stress. The full-length cDNA of the mc5rl-1 was 2143 bp, consisting of a 1224 bp open reading frame encoding (ORF) 408 amino acids. Sequence and phylogenetic analyses revealed that the nucleotide and amino acid sequences of Manila clam mc5rl were highly homologous with mc5r of Crassostrea virginica, Crassostrea gigas, Mizuhopecten yessoensis, and Pecten maximus (32%-36%) and low homologous with vertebrates. The results of the distribution of mc5rl genes showed that mc5rl genes were dominant in the mantle, gonad, and hepatopancreas in R. philippinarum. The expression of mc5rl genes was significantly increased after aerial exposure and low-temperature stress in R. philippinarum in hepatopancreas. Aerial exposure and low-temperature stress could induce mc5rl expressed. Mc5rl might serve as a sensor and promote stress response in R. philippinarum. The cloning and expression characteristics of mc5rl will facilitate the investigation of its function in stress response and other physiological processes in R. philippinarum.