Cryo–electron microscopy structures of human cone visual pigments

Q Qi Peng (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.) J Jian Li H Haihai Jiang (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.) X Xinyu Cheng (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.) P Probal Nag (Department of Physics, Technical University Dortmund, Dortmund, Germany.) G Gunnar Kleinau (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany.) T Trevor D. Lamb (Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.) L Leon Busche (Department of Physics, Technical University Dortmund, Dortmund, Germany.) Q Qiuyuan Lu (Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.) S Sili Zhou (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.) Y Yidi Liu Y Yuting Zhang (Shenzhen Crystalo Biopharmaceutical Co., Ltd., Shenzhen, Guangdong, China.) S Sijia Lv (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.) S Shuangyan Wan (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.) T Tingting Yang (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.) Y Yixiang Chen (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.) W Wei Zhang W Weiwei Nan (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.) Y Ying Fu T Tong Che (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.) Y Yanyan Li (Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.) H Hongfei Liao (Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.) J Jingjing Duan (Sphingolipid Metabolism and Aging, Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, Jiangxi Key Laboratory of Aging and Disease, Nanchang, Jiangxi, China.) I Igor Schapiro (Department of Physics, Technical University Dortmund, Dortmund, Germany.) P Patrick Scheerer (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany.) J Jin Zhang

Abstract

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.

Article Details

Journal Science
Volume / Issue Vol. 392, Issue 6805
Published June 25, 2026
ISSN 0036-8075
Publisher American Association for the Advancement of Science

Journal Info

Science

American Association for the Advancement of Science

ISSN: 0036-8075 Social Sciences

Authors (26)

Q

Qi Peng

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.

J

Jian Li

H

Haihai Jiang

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.

X

Xinyu Cheng

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.

P

Probal Nag

Department of Physics, Technical University Dortmund, Dortmund, Germany.

G

Gunnar Kleinau

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany.

T

Trevor D. Lamb

Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.

L

Leon Busche

Department of Physics, Technical University Dortmund, Dortmund, Germany.

Q

Qiuyuan Lu

Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.

S

Sili Zhou

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.

Y

Yidi Liu

Y

Yuting Zhang

Shenzhen Crystalo Biopharmaceutical Co., Ltd., Shenzhen, Guangdong, China.

S

Sijia Lv

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.

S

Shuangyan Wan

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.

T

Tingting Yang

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.

Y

Yixiang Chen

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.

W

Wei Zhang

W

Weiwei Nan

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.

Y

Ying Fu

T

Tong Che

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.

Y

Yanyan Li

Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.

H

Hongfei Liao

Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

J

Jingjing Duan

Sphingolipid Metabolism and Aging, Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, Jiangxi Key Laboratory of Aging and Disease, Nanchang, Jiangxi, China.

I

Igor Schapiro

Department of Physics, Technical University Dortmund, Dortmund, Germany.

P

Patrick Scheerer

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany.

J

Jin Zhang