allosteric antagonism of insect odorant receptor ion channels变构拮抗昆虫气味受体离子通道.pdfVIP

Allosteric Antagonism of Insect Odorant Receptor Ion Channels 1¤a 1 2 1 2¤b Patrick L. Jones , Gregory M. Pask , Ian M. Romaine , Robert W. Taylor , Paul R. Reid , Alex G. 2,3 2 1,2,3,4 Waterson , Gary A. Sulikowski , Laurence J. Zwiebel * 1 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America, 2 Department of Chemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, United States of America, 3 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 4 Center for Molecular Neuroscience, Institute of Global Health and Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America Abstract Background: At a molecular level, insects utilize members of several highly divergent and unrelated families of cell-surface chemosensory receptors for detection of volatile odorants. Most odors are detected via a family of odorant receptors (ORs), which form heteromeric complexes consisting of a well-conserved OR co-receptor (Orco) ion channel and a non-conserved tuning OR that provides coding specificity to each complex. Orco functions as a non-selective cation channel and is expressed in the majority of olfactory receptor neurons (ORNs). As the destructive behaviors of many insects are principally driven by olfaction, Orco represents a novel target for behavior-based control strategies. While many natural and synthetic odorants have been shown to agonize Orco/Or complexes, only a single direct Orco modu