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Although the structure of rhodopsin was solved more than 20 years ago, cone opsin structures have been lacking. Here, we present cryo\u2013electron microscopy structures of the three human cone opsins, each bound to a G protein and all-\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    retinal in the presumed active state. All three cone opsins differ markedly from rhodopsin. Within the retinal binding pocket, we identified a distinct counterion site (LWS- and MWS-opsins) and a ring of serines around the retinal (SWS-opsin). The active cone opsin structures explain how amino acid substitutions fine-tune spectral sensitivity and help clarify the molecular basis of color vision deficiencies and key differences in rod versus cone activation.\n                  <\/jats:p>","DOI":"10.1126\/science.adz8141","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T18:00:46Z","timestamp":1782410446000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Cryo\u2013electron microscopy structures of human cone visual pigments"],"prefix":"10.1126","volume":"392","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0132-3739","authenticated-orcid":true,"given":"Qi","family":"Peng","sequence":"first","affiliation":[{"name":"The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 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Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-6115","authenticated-orcid":true,"given":"Trevor D.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Busche","sequence":"additional","affiliation":[{"name":"Department of Physics, Technical University Dortmund, Dortmund, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sili","family":"Zhou","sequence":"additional","affiliation":[{"name":"The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidi","family":"Liu","sequence":"additional","affiliation":[{"name":"The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Crystalo Biopharmaceutical Co., Ltd., Shenzhen, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Lv","sequence":"additional","affiliation":[{"name":"The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangyan","family":"Wan","sequence":"additional","affiliation":[{"name":"The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical 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Nanchang, Jiangxi, China."},{"name":"Jiangxi Province Key Laboratory of Pharmacology of Traditional Chinese Medicine, School of Pharmacy, Department of Ophthalmology, the First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8109-7574","authenticated-orcid":true,"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China."},{"name":"Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1955-6570","authenticated-orcid":true,"given":"Hongfei","family":"Liao","sequence":"additional","affiliation":[{"name":"Affiliated Eye Hospital, Jiangxi Medical College, 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