Structural insight into the MC4R conformational changes via different agonist-mediated receptor signaling.

Yang Y, Chen M, Dimmitt R, Harmon CM

Biochemistry6 Nov 2014Cited by 4 (Europe PMC)

PMID25347793DOI10.1021/bi500856xPepBankPUB-25347793

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study4

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone4

In this study, Melanotan I (afamelanotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Melanotan I (afamelanotide).

01LabNot a test of Melanotan I (afamelanotide) aloneIn vitro (cells)Mechanism
In cells expressing mutant MC4R, most single or double mutations did not significantly alter NDP-MSH-induced cAMP production compared with wild-type MC4R.
In plain wordsIn lab cells, most changes made to the MC4R receptor did not change how strongly NDP-MSH switched on cAMP signalling.
Peptide
Melanotan I (afamelanotide)
Outcome
No significant changeNDP-MSH-induced cAMP production in single and double MC4R mutants
Study
n: not reported in source
Cells expressing wild-type and mutant MC4R
Comparator
Wild-type MC4R
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
single or double mutations of the MC4R did not significantly alter cAMP production induced by NDP-MSH compared to that of wild-type MC4R
1 context sentence(design, population, supporting numbers)
Summary · context
We generated and tested 11 single and 8 double mutations that are located at the end of TM3 and beginning of TM6 in MC4R.
In this study, Melanotan I (afamelanotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan I (afamelanotide).
Report a problemFND-2534779301
02LabNot a test of Melanotan I (afamelanotide) aloneIn vitro (cells)Mechanism
In cells expressing the 243H MC4R mutant, cAMP production mediated by NDP-MSH was significantly decreased, due to low receptor expression at the cell surface.
In plain wordsIn lab cells, one MC4R receptor mutant gave less NDP-MSH-induced cAMP signalling because few receptors reached the cell surface.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseNDP-MSH-induced cAMP production in the 243H mutant
Study
n: not reported in source
Cells expressing wild-type and mutant MC4R
Comparator
Wild-type MC4R
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
the mutation 243H significantly decreased cAMP production mediated by NDP-MSH or THIQ due to a low level of receptor expression at the cell surface
1 context sentence(design, population, supporting numbers)
Summary · context
We generated and tested 11 single and 8 double mutations that are located at the end of TM3 and beginning of TM6 in MC4R.
In this study, Melanotan I (afamelanotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan I (afamelanotide).
Report a problemFND-2534779302
03LabNot a test of Melanotan I (afamelanotide) aloneIn vitro (cells)Mechanism
In cells expressing the 247H MC4R mutant, THIQ-mediated cAMP production was significantly decreased but NDP-MSH-mediated production was not.
In plain wordsIn lab cells, one MC4R receptor mutant weakened signalling by the drug THIQ but not by NDP-MSH.
Peptide
Melanotan I (afamelanotide)
Outcome
No significant changeNDP-MSH-induced cAMP production in the 247H mutant
Study
n: not reported in source
Cells expressing wild-type and mutant MC4R
Comparator
Wild-type MC4R
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
the mutation 247H significantly decreased THIQ-mediated cAMP production but not NDP-MSH
1 context sentence(design, population, supporting numbers)
Summary · context
We generated and tested 11 single and 8 double mutations that are located at the end of TM3 and beginning of TM6 in MC4R.
In this study, Melanotan I (afamelanotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan I (afamelanotide).
Report a problemFND-2534779303
04LabNot a test of Melanotan I (afamelanotide) aloneIn vitro (cells)Mechanism
In cells expressing the I150/242H double mutant, Zn(2+) blocked THIQ activation of cAMP signalling but not NDP-MSH activation, suggesting different activated MC4R conformations.
In plain wordsIn lab cells, zinc blocked receptor activation by THIQ but not by NDP-MSH, suggesting the two drugs activate the receptor differently.
Peptide
Melanotan I (afamelanotide)
Outcome
No significant changeNDP-MSH-induced cAMP signalling with Zn(2+) in the I150/242H double mutant
Study
n: not reported in source
Cells expressing wild-type and mutant MC4R
Comparator
Wild-type MC4R
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
the receptor cAMP signaling pathway activation by THIQ is blocked in the presence of Zn(2+) with the double mutation I150/242H but activation by NDP-MSH is not
1 context sentence(design, population, supporting numbers)
Summary · context
We generated and tested 11 single and 8 double mutations that are located at the end of TM3 and beginning of TM6 in MC4R.
In this study, Melanotan I (afamelanotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan I (afamelanotide).
Report a problemFND-2534779304

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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