Olfactory Marker Protein (OMP) Exhibits a β-Clam Fold in Solution: Implications for Target Peptide Interaction and Olfactory Signal Transduction

Abstract

Olfactory marker protein (OMP) is a ubiquitous, cytoplasmic protein found in mature olfactory receptor neurons of all vertebrates. Electrophysiological and behavioral studies demonstrate that it is a modulator of the olfactory signal transduction pathway. Here, we demonstrate that the solution structure of OMP, as determined by NMR studies, is a single globular domain protein comprised of eight β-strands forming two β-sheets oriented orthogonally to one another, thus exhibiting a “β-clam” or “β-sandwich” fold: β-sheet 1 is comprised of β3–β8–β1–β2 and β-sheet 2 contains β6–β5–β4–β7. Insertions include two, long α-helices located on opposite sides of the β-clam and three flexible loops. The juxtaposition of β-strands β6–β5–β4–β7–β2–β1–β8–β3 forms a continuously curved surface and encloses one side of the β-clam. The “cleft” formed by the two β-sheets is opposite to the closed end of the β-clam. Using a peptide titration series, we have identified this cleft as the binding surface for a peptide derived from the Bex1 protein. The highly conserved Ω-loop structure adjacent to the Bex1 peptide-binding surface found in OMP may be the site of additional OMP–protein interactions related to its role in modulating olfactory signal transduction. Thus, the interaction between the OMP and Bex1 proteins could facilitate the interaction between OMP and other components of the olfactory signaling pathway.