Neuromedin C binds Cu(II) and Ni(II) via the ATCUN motif: implications for the CNS and cancer growth.
Neuromedin C is a bombesin-like neuropeptide of the sequence Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2. Characterization of the amino terminal Cu(II), Ni(II) binding motif in albumins led us to predict that any other peptides or proteins with the same motif would also bind Cu(II) and Ni(II) specifically (1). The primary sequence of neuromedin C contains the motif in the form Gly-Asn-His. Neuromedin C was therefore predicted to bind Cu(II) and Ni(II) specifically. The studies presented here confirm that prediction. These findings may have implications for the transport of Cu(II) within the central nervous system as well as both Menkes disease and Wilson disease. Both are genetic copper metabolism disorders which are characterized by severe neurological symptoms. In addition, Cu(II) may interfere with the neurotransmission or growth factor effects of neuromedin C.
Harford
C
C
Department of Biochemistry Research, Hospital for Sick Children, Toronto, Ont.
Sarkar
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001839:Bombesin / Q000737:chemistry* / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism*; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000473:pathology*; D009532:Nickel / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013053:Spectrophotometry
D010446:Peptide Fragments; D011506:Proteins; D003300:Copper; D009532:Nickel; C040794:neuromedin C; D001839:Bombesin