Presentation Details
| Engineering Insect Odorant Receptors Towards Volatiles of Interest Rhodry Brown, Hiroaki Matsunami. Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA |
Abstract
Odorant Receptors (ORs) are sensitive chemical receptors that can respond to a diverse array of volatile chemicals. In insects, ORs are ion channels, containing four, seven-transmembrane domain subunits capable of mixing and matching. Most insects have a highly conserved OR co-receptor. The ORco does not respond to ligands itself but is key for conferring stability by mixing with diversive ORx subunits that respond to volatile compounds. The heterotetramers formed by this combination are the backbone of olfaction in insects. However, not all insects have an ORco, and one notable exception is the Jumping Bristletail (Machilis hrabei). M. hrabei was found to be quite a basal insect, only containing five ORs with no ORco. Through previous work, two of these ORs show significant expression and function in modern cell culture-based systems. Additionally, the structure of one of these ORs, MhOR5, was experimentally elucidated, providing the most accurate data for chemical interactions inside the receptor. Therefore, our work has used MhOR5 as a backbone to understand the ligand binding properties of insect ORs. We created a panel of diverse, human-relevant volatile chemicals and tested them against MhOR5 and an array of mutants to build a better understanding of the contribution of binding pocket residues towards ligand binding and receptor activation. Furthermore, we are engineering a system to mutate and characterize MhOR5 to specific ligands in a manner that creates combinatorial mutants in a non-biased, high-throughput approach. This work is the beginning of an understanding of how ligands selectively activate insect ORs, and what structural features contribute to binding and activation. This data will be key in the engineering of ORs towards volatiles of human interest.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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