Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors

By Thomas A. Hopf, Satoshi Morinaga, S. Ihara, K. Touhara, Debora Marks, Richard Benton. 2015

128 citations recorded by the source corpus.

Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection. The structure of insect odorant receptors (ORs) has remained elusive due to their lack of homology to other proteins and the inability to obtain OR crystals. Here, the authors use amino acid evolutionary covariation patterns to fold these proteins de novoand generate the first three-dimensional models of insect ORs.

Subfields: Cellular and Molecular Neuroscience, Ecology, Evolution, Behavior and Systematics, Genetics

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Citations in the corpus

Large-scale determination of previously unsolved protein structures using evolutionary information (2015, methodology): “…from such predictions have been used to model a wide range of unknown protein structures ( Hayat et al., 2014 ; Wickles et al., 2014 ; Abriata, 2015 ; Antala et al., 2015 ; Hopf et al., 2015 ; Tian et al., 2015 ) and protein–protein complexes ( Ovchinnikov et al., 2014 ; Hopf et al., 2014 ).”
Synthetic protein alignments by CCMgen quantify noise in residue-residue contact prediction (2018, methodology): “…in statistical physics, led to a breakthrough in de-novo (template-free) protein structure prediction: The predicted contacts proved suﬃ-ciently accurate to be used as spatial restraints to reli-25 ably predict protein 3D structures purely from sequence information [23, 26–28, 32, 35, 36, 44–47].”
Insect olfaction and the evolution of receptor tuning (2015, background): “In Culex quinquefasciatus, the oviposition attractants indole (Pelletier et al., 2010) and skatole (Hughes et al., 2010) are detected by specific receptors (OR2 and OR10, respectively), although only 23 compounds were tested in these two studies (see also Bohbot and Dickens, 2012; Bohbot and…”