Structural insights into spectral tuning and retinal exchange in cone visual pigments
Color vision in catarrhine primates relies on red-, green-, and blue-sensitive cone pigments that share an 11- cis -retinal chromophore but differ in absorption maxima. Red and green pigments arose by recent gene duplication and differ at only a few residues. Here, we report cryo–electron microscopy structures of red and green cone pigments from the cynomolgus macaque ( Macaca fascicularis ) integrated with low-temperature vibrational spectroscopy and quantum mechanical and molecular mechanical modeling. The red-green spectral shift is dominated by threonine 285, the hydroxyl dipole of which modulates chromophore electrostatics, whereas steric effects appear modest. We also identified membrane-facing lateral openings in cone pigments but not in inactive rhodopsin. Comparisons with active-state structures suggest activation-dependent gating, and mutational and spectroscopic analyses support a role for this opening in retinal uptake and rapid pigment regeneration.
Authors
- Asato Kojima
- So Iwata (ORCID: https://orcid.org/0000-0003-1735-2937)
- Filippo Sacchetta (ORCID: https://orcid.org/0000-0002-5465-3432)
- Masahiro Fukuda (ORCID: https://orcid.org/0000-0002-8824-846X)
- Eriko Nango (ORCID: https://orcid.org/0000-0001-9851-7355)
- Hideki Kandori (ORCID: https://orcid.org/0000-0002-4922-1344)
- Takeshi Noda (ORCID: https://orcid.org/0000-0002-0658-4663)
- Suhyang Kim (ORCID: https://orcid.org/0000-0002-2817-1202)
- Hiroo Imai (ORCID: https://orcid.org/0000-0003-0729-0322)
- Xuchun Yang (ORCID: https://orcid.org/0000-0002-1500-1773)
- Sayaka Ohashi
- Massimo Olivucci (ORCID: https://orcid.org/0000-0002-8247-209X)
- Nipawan Nuemket (ORCID: https://orcid.org/0009-0005-5252-9488)
- Kazuhiro Kobayashi (ORCID: https://orcid.org/0000-0002-3366-3586)
- Ryoji Suno (ORCID: https://orcid.org/0000-0003-2378-236X)
- Yukihiko Sugita (ORCID: https://orcid.org/0000-0001-6861-4840)
- Kota Katayama (ORCID: https://orcid.org/0000-0001-8498-4374)
- Hideaki Kato (ORCID: https://orcid.org/0000-0002-1941-5535)
- Takuya Kobayashi
Institutions
- University of Siena (IT)
- Kansai Medical University (JP)
- Bowling Green State University (US)
- Tokyo University of the Arts (JP)
- Nagoya Institute of Technology (JP)
- Tohoku University (JP)
- Kyoto University (JP)
- Japan Science and Technology Agency (JP)
- SPring-8 (JP)
- Japan Synchrotron Radiation Research Institute (JP)
- Institut de Biologia Evolutiva (ES)
- The University of Tokyo (JP)
Publication Details
- Journal
- Science
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1126/science.adz3996
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.00