Event:

Animals perceive an enormous diversity of chemicals as smell, primarily detected by odorant receptors (ORs), one of the largest gene families, with many species carrying over 1,000 genes. Despite their discovery more than 30 years ago, only recently have the structural mechanisms of odor recognition begun to emerge. Class I ORs typically respond to carboxylic acids, while Class II ORs, which constitute most terrestrial vertebrate ORs, detect a broader odorant spectrum.

We determined atomic-level structures of Class I ORs bound to carboxylic acids and, using consensus protein design, engineered Class II ORs that could be expressed, purified, and analyzed by cryo-EM. Structures of three Class II ORs revealed both common and distinct binding-pocket features compared to Class I ORs. Together with mutagenesis and computational simulations, these studies outline the molecular logic of odor recognition.

In birds, once thought olfactory-poor, we show that genomes often encode hundreds to thousands of ORs, with the kiwi possessing the most known in any animal. Most belong to a bird-specific gamma-c subfamily of ORs, likely shaped by extensive gene conversion. We confirm avian OR expression in olfactory neurons and identify ligands, revealing gamma-c OR functions. These findings reveal a previously underappreciated role of olfaction in birds and highlight gene conversion as a distinctive evolutionary force shaping their receptor repertoire.