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Cited by 40Receptor Mechanisms and SignalingRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar melanocortin 1 receptor agonist

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Ericson, Mark D., Schnell, Sathya M., Freeman, Katie T., Haskell-Luevano, Carrie·2015·Bioorganic & Medicinal Chemistry Letters
DOI 10.1016/j.bmcl.2015.09.046PMC PMC4628882
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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 α-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 α-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 μM 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.

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  • Gut microbes can produce protein sequences of ≥5 amino acids that share arrangement identical to various appetite-regulating peptides in host.

    “Gut microbes can produce protein sequences of ≥5 amino acids that share an arrangement identical to various appetite-regulating peptides in the host (Ericson et al., 2015;Fetissov et al., 2008), which could trigger the production of immunoglobulins.”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Ericson et al., 2015

    The passage labeled Abstract (page not provided) describes a five-amino-acid overlap between E. coli ClpB and α-MSH, an appetite-regulating peptide, and proposes that ClpB may contribute to α-MSH antibody production. The overlap is explicitly discontinuous; the paper does not establish identical sequences of five or more amino acids across various host appetite-regulating peptides or multiple gut microbes. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Ericson, M. D., Schnell, S. M., Freeman, K. T., & Haskell-Luevano, C.
Affiliations
University of Minnesota (US)
ORCID
Venue
Bioorganic & Medicinal Chemistry Letters
Publisher
Elsevier BV
Published
2015-11
Volume
25
Issue
22
Pages
5306-5308
ISSN
0960-894X (ISSN-L)
DOI
10.1016/j.bmcl.2015.09.046
PMC
PMC4628882
OpenAlex
W1692714370
Cited by
40
References
3
Citations by year
2025: 1 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 3
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioorganic & Medicinal Chemistry Letters (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (R01DK097838, R01DK091906)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
ClpB, Escherichia coli, MC1R, heat shock proteins, alpha-melanocyte-stimulating hormone, proopiomelanocortin, receptor agonists, melanocortin 3 receptor, melanocortin-4 receptor, MC5R, receptor fragments, selective ligands
MeSH terms
Amino Acid Sequence, Animals, Escherichia coli, Heat-Shock Proteins, Humans, Ligands, Peptide Fragments, Escherichia coli Proteins, Receptor, Melanocortin, Type 1, Endopeptidase Clp, Mice, HEK293 Cells

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