Characterisation of D117A and H260A mutations in the melanocortin 1 receptor

Helgi B. Schiöth; Ruta Muceniece; Michael Szardenings; Peteris Prusis; Gunnar Lindeberg; Shubh D. Sharma; Victor J. Hruby; Jarl E.S. Wikberg

doi:10.1016/S0303-7207(96)03993-7

Characterisation of D117A and H260A mutations in the melanocortin 1 receptor

Helgi B. Schiöth, Ruta Muceniece, Michael Szardenings, Peteris Prusis, Gunnar Lindeberg, Shubh D. Sharma, Victor J. Hruby, Jarl E.S. Wikberg

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Recent site directed mutagenesis studies on the melanocortin 1 (MC1) receptor have indicated the importance of D117 and H260 amino acid residues for the binding of α-MSH (melanocyte stimulating hormone). Here, we report the testing of 12 cyclic and linear MSH peptides on the D117A and H260A mutant receptors. Moreover, we constructed a double mutant which displayed a major loss in affinity for [Nle⁴, D-Phe⁷]α-MSH. Our new data of His⁶ and Phe⁷ substituted MSH peptides are compared with previous results and the hypothesis of putative interactions of D117 and H260 with single amino acids in the MSH peptide. Our conclusions are that the D117A and the H260A mutations may cause conformational changes in the receptor which can not be linked to any specific amino acid in the MSH-peptides.

Original language	English (US)
Pages (from-to)	213-219
Number of pages	7
Journal	Molecular and Cellular Endocrinology
Volume	126
Issue number	2
DOIs	https://doi.org/10.1016/S0303-7207(96)03993-7
State	Published - Feb 7 1997
Externally published	Yes

Keywords

Ligand binding
MC1 receptor
MSH
Mutagenesis

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology

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10.1016/S0303-7207(96)03993-7

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title = "Characterisation of D117A and H260A mutations in the melanocortin 1 receptor",

abstract = "Recent site directed mutagenesis studies on the melanocortin 1 (MC1) receptor have indicated the importance of D117 and H260 amino acid residues for the binding of α-MSH (melanocyte stimulating hormone). Here, we report the testing of 12 cyclic and linear MSH peptides on the D117A and H260A mutant receptors. Moreover, we constructed a double mutant which displayed a major loss in affinity for [Nle4, D-Phe7]α-MSH. Our new data of His6 and Phe7 substituted MSH peptides are compared with previous results and the hypothesis of putative interactions of D117 and H260 with single amino acids in the MSH peptide. Our conclusions are that the D117A and the H260A mutations may cause conformational changes in the receptor which can not be linked to any specific amino acid in the MSH-peptides.",

keywords = "Ligand binding, MC1 receptor, MSH, Mutagenesis",

author = "Schi{\"o}th, {Helgi B.} and Ruta Muceniece and Michael Szardenings and Peteris Prusis and Gunnar Lindeberg and Sharma, {Shubh D.} and Hruby, {Victor J.} and Wikberg, {Jarl E.S.}",

note = "Funding Information: This study was supported by grants from the Swedish MRC (04X-05957), the CEC (ERBCHRXCT 940505), the Swedish CFN, the Groschinsky foundation, the Howard Hughes Medical Institute (HHMI 75195-548501) and from the US Public Health Service (OK 17420).",

year = "1997",

month = feb,

day = "7",

doi = "10.1016/S0303-7207(96)03993-7",

language = "English (US)",

volume = "126",

pages = "213--219",

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T1 - Characterisation of D117A and H260A mutations in the melanocortin 1 receptor

AU - Schiöth, Helgi B.

AU - Muceniece, Ruta

AU - Szardenings, Michael

AU - Prusis, Peteris

AU - Lindeberg, Gunnar

AU - Sharma, Shubh D.

AU - Hruby, Victor J.

AU - Wikberg, Jarl E.S.

N1 - Funding Information: This study was supported by grants from the Swedish MRC (04X-05957), the CEC (ERBCHRXCT 940505), the Swedish CFN, the Groschinsky foundation, the Howard Hughes Medical Institute (HHMI 75195-548501) and from the US Public Health Service (OK 17420).

PY - 1997/2/7

Y1 - 1997/2/7

N2 - Recent site directed mutagenesis studies on the melanocortin 1 (MC1) receptor have indicated the importance of D117 and H260 amino acid residues for the binding of α-MSH (melanocyte stimulating hormone). Here, we report the testing of 12 cyclic and linear MSH peptides on the D117A and H260A mutant receptors. Moreover, we constructed a double mutant which displayed a major loss in affinity for [Nle4, D-Phe7]α-MSH. Our new data of His6 and Phe7 substituted MSH peptides are compared with previous results and the hypothesis of putative interactions of D117 and H260 with single amino acids in the MSH peptide. Our conclusions are that the D117A and the H260A mutations may cause conformational changes in the receptor which can not be linked to any specific amino acid in the MSH-peptides.

AB - Recent site directed mutagenesis studies on the melanocortin 1 (MC1) receptor have indicated the importance of D117 and H260 amino acid residues for the binding of α-MSH (melanocyte stimulating hormone). Here, we report the testing of 12 cyclic and linear MSH peptides on the D117A and H260A mutant receptors. Moreover, we constructed a double mutant which displayed a major loss in affinity for [Nle4, D-Phe7]α-MSH. Our new data of His6 and Phe7 substituted MSH peptides are compared with previous results and the hypothesis of putative interactions of D117 and H260 with single amino acids in the MSH peptide. Our conclusions are that the D117A and the H260A mutations may cause conformational changes in the receptor which can not be linked to any specific amino acid in the MSH-peptides.

KW - Ligand binding

KW - MC1 receptor

KW - MSH

KW - Mutagenesis

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M3 - Article

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AN - SCOPUS:0031557117

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JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 2

ER -

Characterisation of D117A and H260A mutations in the melanocortin 1 receptor

Abstract

Keywords

ASJC Scopus subject areas

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