{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:20:52Z","timestamp":1788272452538,"version":"build-2803163510"},"reference-count":53,"publisher":"American Chemical Society (ACS)","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["6\/9-7(326)\/2023-ECD-II"],"award-info":[{"award-number":["6\/9-7(326)\/2023-ECD-II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["ANRF\/JBG\/2025\/000434\/LS"],"award-info":[{"award-number":["ANRF\/JBG\/2025\/000434\/LS"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Biotechnology , Ministry of Science and Technology","award":["BT\/RLF\/Re-entry\/09\/2019"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/09\/2019"]}]},{"name":"Department of Biotechnology , Ministry of Science and Technology","award":["PR32713"],"award-info":[{"award-number":["PR32713"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mosquito-borne diseases, particularly malaria, remain a major global health challenge. Among different mosquitoes, Anopheles are solely responsible for malaria. Insecticide-based interventions such as insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are central to mosquito control. However, the widespread emergence of insecticide resistance, especially to pyrethroids, the most commonly used insecticides for mosquito worldwide, threatens their effectiveness. While genetic and metabolic mechanisms of resistance are well characterized, behavioral and sequestration-based mechanisms, particularly those involving chemosensory proteins (CSPs), are less understood. CSPs and odorant-binding proteins (OBPs) are integral components of the mosquito olfactory system, mediating host-seeking and other behavioral processes by transporting odorant molecules to olfactory receptors. Recent evidence suggests that CSPs may also bind insecticides like pyrethroids, contributing to resistance through sequestration. In this study, we investigated the structural and functional roles of CSPs in Anopheles mosquitoes. We determined three high-resolution X-ray crystal structures (apo-form) of CSPs (&amp;lt;2 \u00c5) from Anopheles culicifacies and Anopheles gambiae, representing the first crystal structures of CSPs from any Anopheles species reported to date. Using structural, biophysical and computational approaches, we assessed CSP\u2013ligand recognition of various insecticides, specifically pyrethroids and identified key residues potentially involved in pyrethroid interaction through site-directed mutagenesis. The moderate micromolar binding affinities of deltamethrin and permethrin, compared to other insecticides, support the role of CSPs in pyrethroid sequestration. Our findings offer mechanistic insights into pyrethroid sequestration and provide a foundation for developing novel vector control strategies that target CSP\u2013insecticide interactions to combat pyrethroid resistance.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00114","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:57:49Z","timestamp":1788202669000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural Insights\ninto Pyrethroid Recognition by\n                    <i>Anopheles<\/i>\n                    Chemosensory Proteins"],"prefix":"10.1021","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2180-9891","authenticated-orcid":true,"given":"Shibani","family":"Biswas","sequence":"first","affiliation":[{"name":"ICMR-National Institute of Malaria Research (NIMR) , Dwarka , ,","place":["New Delhi, India, 110077"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , , ,","place":["Ghaziabad, Uttar Pradesh, India, 201002"]},{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , , Aruna Asaf Ali Marg , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogavel","family":"Manickam","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , , Aruna Asaf Ali Marg , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choong Yeu","family":"Khai","sequence":"additional","affiliation":[{"name":"National University of Singapore , , 14 Science Drive 4 , ,","place":["Singapore, Singapore, 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Goswami","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Malaria Research (NIMR) , Dwarka , ,","place":["New Delhi, India, 110077"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , , ,","place":["Ghaziabad, Uttar Pradesh, India, 201002"]},{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , , Aruna Asaf Ali Marg , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-3600","authenticated-orcid":true,"given":"Sanskrita","family":"Sukla","sequence":"additional","affiliation":[{"name":"National University of Singapore , , 14 Science Drive 4 , ,","place":["Singapore, Singapore, 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosicler","family":"Barbosa","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory , 71 Avenue des Martyrs , ,","place":["Grenoble, France, 38000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihyun","family":"Sung","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory , 71 Avenue des Martyrs , ,","place":["Grenoble, France, 38000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rini","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences , , ,","place":["New Delhi, India, 110029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 Antonio","family":"Ma\u0301rquez","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory , 71 Avenue des Martyrs , ,","place":["Grenoble, France, 38000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9199-4367","authenticated-orcid":true,"given":"Aditya","family":"Chaki","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , , Aruna Asaf Ali Marg , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-0034","authenticated-orcid":true,"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , , Aruna Asaf Ali Marg , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Das","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Malaria Research (NIMR) , Dwarka , ,","place":["New Delhi, India, 110077"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , , ,","place":["Ghaziabad, Uttar Pradesh, India, 201002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9781-5326","authenticated-orcid":true,"given":"J.","family":"Sivaraman","sequence":"additional","affiliation":[{"name":"National University of Singapore , , 14 Science Drive 4 , ,","place":["Singapore, Singapore, 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7384-690X","authenticated-orcid":true,"given":"Soumyananda","family":"Chakraborti","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District , , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026090104520514800_cit1","volume-title":"Fact Sheet on Vector-Borne Diseases","author":"World Health Organisation.","year":"2024"},{"key":"2026090104520514800_cit2","unstructured":"World Health Organisation.\n          .  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J. Biochem."},{"issue":"3","key":"2026090104520514800_cit21","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/0965-1748(95)00096-8","article-title":"Binding proteins from\nthe antennae of Bombyx mori","volume":"26","author":"Krieger","year":"1996","journal-title":"Insect Biochem.\nMol. Biol."},{"issue":"23","key":"2026090104520514800_cit22","doi-asserted-by":"publisher","first-page":"16340","DOI":"10.1016\/S0021-9258(17)34013-9","article-title":"Putative Drosophila\npheromone-binding proteins expressed in a subregion of the olfactory\nsystem","volume":"269","author":"McKenna","year":"1994","journal-title":"J. Biol. 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Genes Evol."},{"issue":"7790","key":"2026090104520514800_cit25","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s41586-019-1864-1","article-title":"A sensory\nappendage\nprotein protects malaria vectors from pyrethroids","volume":"577","author":"Ingham","year":"2020","journal-title":"Nature"},{"key":"2026090104520514800_cit26","doi-asserted-by":"publisher","first-page":"105393","DOI":"10.1016\/j.pestbp.2023.105393","article-title":"Chemosensory\nproteins are associated with thiamethoxam tolerance in bird cherry-oat\naphid Rhopalosiphum padi","volume":"192","author":"Gao","year":"2023","journal-title":"Pestic. Biochem. Physiol."},{"key":"2026090104520514800_cit27","doi-asserted-by":"publisher","first-page":"105076","DOI":"10.1016\/j.pestbp.2022.105076","article-title":"Chemosensory proteins confer adaptation\nto the ryanoid\nanthranilic diamide insecticide cyantraniliprole in Aphis gossypii\nglover","volume":"184","author":"Xu","year":"2022","journal-title":"Pestic. Biochem. Physiol."},{"issue":"3","key":"2026090104520514800_cit28","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1021\/acs.jafc.2c05973","article-title":"Evidence for the Participation of\nChemosensory Proteins in Response to Insecticide Challenge in Conopomorpha sinensis","volume":"71","author":"Yao","year":"2023","journal-title":"J. Agric. Food\nChem."},{"issue":"7","key":"2026090104520514800_cit29","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1002\/ps.7415","article-title":"The chemosensory protein\n1 contributes to indoxacarb resistance in Plutella xylostella (L.)","volume":"79","author":"Li","year":"2023","journal-title":"Pest Manage. 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Physiol."},{"issue":"31","key":"2026090104520514800_cit33","doi-asserted-by":"publisher","first-page":"19340","DOI":"10.1021\/acs.jafc.5c05054","article-title":"Structural and Transcriptional\nPlasticity of OBP3 Confers Insecticide Adaptation in Spodoptera litura","volume":"73","author":"Deng","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"2026090104520514800_cit34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190412","article-title":"Comparative\ngenomics of chemosensory protein genes (CSPs) in twenty-two mosquito\nspecies (Diptera: Culicidae): Identification, characterization, and\nevolution","volume":"13","author":"Mei","year":"2018","journal-title":"PLoS ONE"},{"issue":"2","key":"2026090104520514800_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/npp2.70008","article-title":"Insect chemosensory proteins as targets in insecticide resistance\nand development","volume":"2","author":"Li","year":"2025","journal-title":"New Plant Protection"},{"key":"2026090104520514800_cit36","doi-asserted-by":"publisher","first-page":"7032","DOI":"10.1002\/ps.70061","article-title":"Identification\nof chemosensory protein inhibitors as a potential strategy to combat\npyrethroid resistance in Anopheles gambiae","volume":"81","author":"Liu","year":"2025","journal-title":"Pest Manage. Sci."},{"issue":"1","key":"2026090104520514800_cit37","doi-asserted-by":"publisher","first-page":"37696","DOI":"10.1038\/s41598-025-21404-9","article-title":"Olfactory\ngene dynamics in invasive Indian and non-invasive\nAfrican malaria vectors at the crossroads of development, infection\nand resistance","volume":"15","author":"Sharma","year":"2025","journal-title":"Sci. Rep"},{"issue":"17","key":"2026090104520514800_cit38","doi-asserted-by":"publisher","first-page":"4731","DOI":"10.1046\/j.1432-1327.2001.02398.x","article-title":"Chemosensory\nprotein from the moth Mamestra brassicae: Expression\nand secondary structure from1 H and15 N NMR","volume":"268","author":"Campanacci","year":"2001","journal-title":"Eur. J. Biochem."},{"issue":"35","key":"2026090104520514800_cit39","doi-asserted-by":"publisher","first-page":"32094","DOI":"10.1074\/jbc.M204371200","article-title":"X-ray Structure and Ligand Binding\nStudy of a Moth Chemosensory Protein","volume":"277","author":"Lartigue","year":"2002","journal-title":"J. Biol.\nChem."},{"issue":"9","key":"2026090104520514800_cit40","doi-asserted-by":"publisher","first-page":"5069","DOI":"10.1073\/pnas.0836654100","article-title":"Moth chemosensory protein exhibits\ndrastic conformational changes and cooperativity on ligand binding","volume":"100","author":"Campanacci","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"35","key":"2026090104520514800_cit41","doi-asserted-by":"publisher","first-page":"10606","DOI":"10.1021\/bi060998w","article-title":"Solution Structure\nof a Chemosensory\nProtein from the Desert Locust Schistocerca gregaria","volume":"45","author":"Tomaselli","year":"2006","journal-title":"Biochemistry"},{"issue":"3","key":"2026090104520514800_cit42","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/arch.20205","article-title":"Structure of Bombyx mori chemosensory protein 1 in solution","volume":"66","author":"Jansen","year":"2007","journal-title":"Arch.\nInsect Biochem. Physiol."},{"issue":"7","key":"2026090104520514800_cit43","doi-asserted-by":"publisher","first-page":"602","DOI":"10.3390\/insects12070602","article-title":"The Crystal Structure\nof the Spodoptera litura Chemosensory Protein CSP8","volume":"12","author":"Jia","year":"2021","journal-title":"Insects"},{"issue":"1","key":"2026090104520514800_cit44","doi-asserted-by":"publisher","first-page":"8073","DOI":"10.1038\/srep08073","article-title":"Chemosensillum\nimmunolocalization\nand ligand specificity of chemosensory proteins in the alfalfa plant\nbug Adelphocoris lineolatus (Goeze)","volume":"5","author":"Sun","year":"2015","journal-title":"Sci. Rep"},{"issue":"3","key":"2026090104520514800_cit45","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1387\/ijdb.1445782","article-title":"Purification and localization\nof p10, a novel protein that increases in nymphal regenerating legs\nof Periplaneta americana (American cockroach)","volume":"36","author":"Nomura","year":"1992","journal-title":"Int. J. Dev. Biol."},{"issue":"5","key":"2026090104520514800_cit46","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1023\/B:JOEC.0000028457.51147.d4","article-title":"Analysis of the Insect OS-D-Like Gene Family","volume":"30","author":"Wanner","year":"2004","journal-title":"J. Chem. 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Biol."},{"key":"2026090104520514800_cit49","doi-asserted-by":"publisher","first-page":"106647","DOI":"10.1016\/j.pestbp.2025.106647","article-title":"Structural\nplasticity underlies the binding capacities\nand specificities of chemosensory proteins towards various pesticides","volume":"215","author":"Zhang","year":"2025","journal-title":"Pestic. Biochem. 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