title: Is the olfactory receptor a metalloprotein?
abstract: The sense of smell is arguably our most primal faculty and also the least understood. Even our own olfactorily impaired species is capable of detecting approximately 10,000 distinct scents [Buck, L. & Axel, R. (1991) Cell 65, 175-187]. To achieve that amazing diversity, mammals have approximately 1,000 olfactory genes, which accounts for approximately 3% of their entire genome [Mombaerts, P. (1999) Science 286, 707-711]. The olfactory receptors (ORs) are believed to be seven-helix transmembrane proteins, with an odorant-binding site on the periplasmic domain and a G protein-binding site on the cytoplasmic domain. Odorants first bind to an OR, which then undergoes some structural change that triggers the G protein activation and the following cascade of events leading to nerve cell activity. The structural details of ORs, however, remain to be determined. In this paper, we will describe a hypothesis in which metal ions play an important role for odorant recognition. We analyze the predicted structure and consensus sequence of the ORs and propose a metal-binding site in the loop between fourth and fifth helix (4-5 loop). We have prepared synthetically a pentapeptide that contains this putative binding site and find that it not only has high affinity for binding Cu(II) and Zn(II) ions, but that it also undergoes a dramatic transition to an alpha-helical structure upon metal ion binding. Based on these observations, we propose a "shuttlecock" mechanism for the possible structural change in ORs upon odorant binding. This mechanism involves membrane penetration of the 4-5 loop after residue charge neutralization by metal ion binding.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Jiangyun
authors.initials: J
authors.lastname: Wang
authors.forename: Zaida A
authors.initials: ZA
authors.lastname: Luthey-Schulten
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Suslick
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D008390:Markov Chains; D008667:Metalloproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009812:Odorants; D017433:Protein Structure, Secondary; D018035:Receptors, Odorant / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
chemical_list: D008667:Metalloproteins; D018035:Receptors, Odorant