Cryo–electron microscopy structures of human cone visual pigments
Human trichromatic color vision relies on three cone opsins [long-, middle-, and short-wavelength-sensitive opsins (LWS-, MWS-, and SWS-opsins, respectively)], whereas scotopic rod vision is mediated by rhodopsin. Although the structure of rhodopsin was solved more than 20 years ago, cone opsin structures have been lacking. Here, we present cryo–electron microscopy structures of the three human cone opsins, each bound to a G protein and all- trans 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.
Authors
- Probal Nag (ORCID: https://orcid.org/0000-0001-7414-1824)
- Gunnar Kleinau (ORCID: https://orcid.org/0000-0003-2131-671X)
- Xinyu Cheng (ORCID: https://orcid.org/0009-0007-3641-8336)
- Igor Schapiro (ORCID: https://orcid.org/0000-0001-8536-6869)
- Weiwei Nan
- Jingjing Duan (ORCID: https://orcid.org/0000-0003-2716-2627)
- Trevor D. Lamb (ORCID: https://orcid.org/0000-0003-0299-6115)
- Tingting Yang (ORCID: https://orcid.org/0000-0002-5220-588X)
- Sili Zhou
- Patrick Scheerer (ORCID: https://orcid.org/0000-0001-5028-2075)
- Hongfei Liao (ORCID: https://orcid.org/0000-0003-1955-6570)
- Tong Che (ORCID: https://orcid.org/0009-0000-7871-5688)
- Haihai Jiang
- Peng Qi (ORCID: https://orcid.org/0000-0002-1795-2185)
- Yanyan Li (ORCID: https://orcid.org/0000-0002-8109-7574)
- Jian Li (ORCID: https://orcid.org/0000-0001-9511-4219)
- Jin Zhang (ORCID: https://orcid.org/0000-0002-9705-0033)
- Wei Zhang (ORCID: https://orcid.org/0000-0001-7800-3189)
- Ying Liu (ORCID: https://orcid.org/0000-0002-1312-0146)
- Ying Fu (ORCID: https://orcid.org/0000-0002-6677-694X)
- Shuangyan Wan
- Sijia Lv (ORCID: https://orcid.org/0009-0009-2943-4113)
- Ye Chen (ORCID: https://orcid.org/0009-0008-8598-5860)
- Yuting Zhang (ORCID: https://orcid.org/0000-0001-6265-7452)
- Qiuyuan Lu
- Leon Busche
Institutions
- Australian National University (AU)
- Nanchang University (CN)
- Hebrew University of Jerusalem (IL)
- TU Dortmund University (DE)
- Southern University of Science and Technology (CN)
- Shenzhen Bioeasy Biotechnology (China) (CN)
- First Affiliated Hospital of Jiangxi Medical College (CN)
- Third Affiliated Hospital of Nanchang University (CN)
- First Affiliated Hospital of Gannan Medical University (CN)
- Institute of Aging (CA)
- Charité - Universitätsmedizin Berlin (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Science
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1126/science.adz8141
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Guangdong Innovative and Entrepreneurial Research Team Program
- Natural Science Foundation of Shenzhen City
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- National Natural Science Foundation of China
- Israel Science Foundation
- Natural Science Foundation of Jiangxi Province
- National Key Research and Development Program of China