Abstract
Odorant receptors (ORs) are essential for insect survival in the environment and thus are ideal molecular targets for the design of insect-inspired modern green chemicals to control populations of agricultural pests and insects of medical importance. Although insect ORs are known for more than a decade, their structural biology is still in its infancy. Here, we unravel the first structural features of ORs from the malaria mosquito, the Southern house mosquito and the silkworm moth. The second extracellular loops (ECL-2s) of their predicted structures are much longer than ECL-1s and ECL-3s. The 27 amino-acid-residue-long of the ECL-2s in mosquito and the 43 amino-acid-residue-long ECL2s in moth ORs are well-conserved. About one-third of the residues are identical, including 3–4 Pro residues. Thorough examination of well-conserved residues in these structures, by point mutation and functional assay with the Xenopus oocyte recording system, strongly suggest that these “loops” include three β-turns and some degree of folding. In the Southern house mosquito three Pro residues in ECL-2 are essential for full activation of the receptor, which is finely tuned to the oviposition attractant 3-methylindole. Additionally, the “corner residues” of prolines, including Gly, Tyr, and Leu are functionally important thus suggesting that turns are stabilized not only by backbone hydrogen bonds, but also by side–chain interactions. Examination of ECL-2s from a distant taxonomical group suggests these ECL-2 loops might be functionally important in all insect ORs. Two of the four Pro residues in the predicted ECL-2 of the bombykol receptor in the silkworm moth, BmorOR1, are essential for function. Experimental evidence indicates that these loops may not be specificity determinants, but they may form a cover to the yet-to-be-identified membrane embedded binding cavities of insect ORs.
Highlights
Insects negatively affect human society when they become agricultural pests that damage our crops and stored products or vectors of diseases that cause tragic human suffering and death [1,2,3]
We focused on odorant receptors (ORs) from three mosquito species, which have been reported to respond to indoles, indole and 3-methylindole [15,16,17,18,19]: AgamOR10, CquiOR10, AaegOR10, AgamOR2, CquiOR2, and AaegOR2
We compared the OR from the silkworm moth, BmorOR1, which is sensitive to the sex pheromone bombykol [20,21] with the ORs from three moth species, Heliothis virescens, Diaphania indica, and Plutella xylostella
Summary
Insects negatively affect human society when they become agricultural pests that damage our crops and stored products or vectors of diseases that cause tragic human suffering and death [1,2,3]. We know that insect ORs are not GPCRs, as initially envisioned [4] They are seven-transmembrane proteins with inverse topology [5], i.e., intracellular N-terminus and extracellular C-terminus. ORs led to the hypothesis that a binding pocket is located on the extracellular halves of its transmembrane (TM) domains [11] It has been shown by using substitute cysteine accessibility method that a residue located at the predicted interface between the transmembrane segment-3 and extracellular loop-2 (ECL- 2) plays a role in activation of a Drosophila OR [12]. We probed 16 mutated and 3 wild type ORs by using the Xenopus expression system to identify functionally important residues in ECL-2 loops in ORs from the malaria mosquito, Anopheles gambiae and the Southern house mosquito, Culex quinquefasciatus, as well as the silkworm moth, Bombyx mori
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