Proadrenomedullin N-terminal peptide and cortistatin activation of MrgX2 receptor is based on a common structural motif.
The G protein-coupled receptor MrgX2 belongs to the large family of the Mas-related genes or sensory neuron-specific G protein-coupled receptors. The MrgX2 receptor has been shown to be activated by the peptides cortistatin and proadrenomedullin N-terminal peptides (PAMP). Here we investigated the structure activity relationship of PAMP and identified key structural features that are shared with cortistatin and might explain why two apparently unrelated peptides are able to activate a single G protein-coupled receptor.
Nothacker
Hans-Peter
HP
Department of Pharmacology, 354 MedSurge II University of California, Irvine, Irvine CA 92697-4625, USA. hnothack@uci.edu
Wang
Zhiwei
Z
Zeng
Hua
H
Mahata
Sushil K
SK
O'Connor
Daniel T
DT
Civelli
Olivier
O
D053607:Adrenomedullin; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism*
C480039:MRGPRX2 protein, human; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011498:Protein Precursors; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C099323:cortistatin; C088633:proadrenomedullin; D053607:Adrenomedullin