The common C-terminal sequences of substance P and neurokinin A contact the same region of the NK-1 receptor

Andrew A. Bremer, Susan E. Leeman, Norman D. Boyd

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Although neurokinin A (NKA), a tachykinin peptide with sequence homology to substance P (SP), is a weak competitor of radiolabeled SP binding to the NK-1 receptor (NK-1R), more recent direct binding studies using radiolabeled NKA have demonstrated an unexpected high-affinity interaction with this receptor. To document the site of interaction between NKA and the NK-1R, we have used a photoreactive analogue of NKA containing p-benzoyl-L-phenylalanine (Bpa) substituted in position 7 of the peptide. Peptide mapping studies of the receptor photolabeled by 125I-iodohistidyl1-Bpa7NKA have established that the site of photoinsertion is located within a segment of the receptor extending from residues 178 to 190 (VVCMIEWPEHPNR). We have previously shown that 125I-BH-Bpa8SP, a photoreactive analogue of SP, covalently attaches to M181 within this same receptor sequence. Importantly, both of these peptides (125I-iodohistidyl1-Bpa7NKA and 125I-BH-Bpa8SP) have the photoreactive amino acid in an equivalent position within the conserved tachykinin carboxyl-terminal tail. In this report, we also show that site-directed mutagenesis of M181 to A181 in the NK-1R results in a complete loss of photolabeling of both peptides to this receptor site, indicating that the equivalent position of SP and NKA, when bound to the NK-1R, contact the same residue. (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalFEBS Letters
Volume486
Issue number1
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

Keywords

  • Neurokinin A
  • NK-1 receptor
  • Photoaffinity labeling
  • Substance P

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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