8VV3

Structure of the insect gustatory receptor Gr9 from Bombyx mori in complex with L-sorbose

8VV3 の概要

• エントリーDOI: 10.2210/pdb8vv3/pdb
• EMDBエントリー: 42628 42629 43548
• 分子名称: Gustatory receptor, alpha-L-sorbopyranose (2 entities in total)
• 機能のキーワード: gustatory receptor, ion channel, sugar-binding, fructose, transport protein
• 由来する生物種: Bombyx mori (domestic silkworm)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203428.90

構造登録者

Gomes, J.V.,Butterwick, J.A. (登録日: 2024-01-30, 公開日: 2024-03-20, 最終更新日: 2024-05-15)

主引用文献

Gomes, J.V.,Singh-Bhagania, S.,Cenci, M.,Chacon Cordon, C.,Singh, M.,Butterwick, J.A.
The molecular basis of sugar detection by an insect taste receptor.
Nature, 629:228-234, 2024

PubMed Abstract: Animals crave sugars because of their energy potential and the pleasurable sensation of tasting sweetness. Yet all sugars are not metabolically equivalent, requiring mechanisms to detect and differentiate between chemically similar sweet substances. Insects use a family of ionotropic gustatory receptors to discriminate sugars, each of which is selectively activated by specific sweet molecules. To gain insight into the molecular basis of sugar selectivity, we determined structures of Gr9, a gustatory receptor from the silkworm Bombyx mori (BmGr9), in the absence and presence of its sole activating ligand, D-fructose. These structures, along with structure-guided mutagenesis and functional assays, illustrate how D-fructose is enveloped by a ligand-binding pocket that precisely matches the overall shape and pattern of chemical groups in D-fructose. However, our computational docking and experimental binding assays revealed that other sugars also bind BmGr9, yet they are unable to activate the receptor. We determined the structure of BmGr9 in complex with one such non-activating sugar, L-sorbose. While both sugars bind a similar position, only D-fructose is capable of engaging a bridge of two conserved aromatic residues that connects the pocket to the pore helix, inducing a conformational change that allows the ion-conducting pore to open. Thus, chemical specificity does not depend solely on the selectivity of the ligand-binding pocket, but it is an emergent property arising from a combination of receptor-ligand interactions and allosteric coupling. Our results support a model whereby coarse receptor tuning is derived from the size and chemical characteristics of the pocket, whereas fine-tuning of receptor activation is achieved through the selective engagement of an allosteric pathway that regulates ion conduction.

PubMed: 38447670
DOI: 10.1038/s41586-024-07255-w

実験手法

ELECTRON MICROSCOPY (2.61 Å)