Molecular View Sheds Light on the Mechanics of Olfactory Receptors

by Linda Kossoff •

How does an individual olfactory receptor (OR) flexibly recognize diverse odorants in terms of structure and mechanics?

BOTTOM LINE

Diverse odorants appear to share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that endow the olfactory system with its immense discriminatory capacity.

BACKGROUND: The broad tuning of ORs is central to the detection and discrimination of the vast chemical world. Although most individual ORs detect a wide variety of structurally and chemically diverse odorants, without a structural model, how such flexible chemical recognition is achieved remains unknown.

COMMENT: This is a landmark paper for rhinologists, offering structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. This in-depth knowledge of receptor activity paves the way for understanding the evolution of chemical perception, how other neurological systems and processes work, and practical implications, such as the development of targeted drugs and insect repellents. —Subinoy Das, MD

STUDY DESIGN: Insect/animal research study.

SETTING: Laboratory of Neurophysiology and Behavior, The Rockefeller University, New York, N.Y.

SYNOPSIS: Researchers studied the jumping bristletail, whose few ORs belong to a large family of receptors with millions of variants found in many insect species. To understand how a single OR recognizes different chemicals, they focused on the structure of the receptor MhOR 5, alone and bound to the common chemical eugenol or the insect repellent DEET. They discovered that both molecules were bound at the same location in the receptor and fit entirely inside a “pocket,” and that the bonds formed within the OR were weak in nature. The simple geometry of the binding site imposed minimal restriction on the shape of odorants that can bind, accommodating both eugenol and DEET with little structural rearrangement. Authors noted that the receptor was not selective to a specific chemical feature, that other odor molecules could be accommodated in a similar way, and that the receptor is flexible enough to be reconfigured to change the molecules with which it binds. They also stated that odorant detection in mammals has been proposed to also rely on distributed hydrophobic and nondirectional interactions within a deep transmembrane pocket. They conclude that, structurally and mechanistically, distinct receptor families appear to rely on similar principles for their broad chemical tuning.

CITATION: Del Mármol J, Yedlin MA, Ruta V. The structural basis of odorant recognition in insect olfactory receptors. Nature. 2021;597:126-131.