Journal article
Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision
Proceedings of the National Academy of Sciences - PNAS, Vol.122(1), e2419732121
01/07/2025
DOI: 10.1073/pnas.2419732121
PMCID: PMC11725853
PMID: 39739818
Abstract
Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures of human cone PDE6C in various liganded states by single-particle cryo-EM that reveal essential functional dynamics and adaptations of the enzyme. Our analysis exposed the dynamic nature of PDE6C association with its regulatory γ-subunit (Pγ) which allows openings of the catalytic pocket in the absence of phototransduction signaling, thereby controlling photoreceptor noise and sensitivity. We demonstrate evolutionarily recent adaptations of PDE6C stemming from residue substitutions in the Pγ subunit and the noncatalytic cGMP binding site and influencing the Pγ dynamics in holoPDE6C. Thus, our structural analysis sheds light on the previously unrecognized molecular evolution of the effector enzyme in cones that advances adaptation for photopic vision.
Details
- Title: Subtitle
- Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision
- Creators
- Sneha Singh - University of IowaDhiraj Srivastava - University of IowaKimberly Boyd - University of IowaNikolai O Artemyev - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.122(1), e2419732121
- DOI
- 10.1073/pnas.2419732121
- PMID
- 39739818
- PMCID
- PMC11725853
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- NATL ACAD SCIENCES
- Grant note
- N/A / Knights Templar Eye Foundation (KTEF) EY-10843 / HHS | NIH | National Eye Institute (NEI)
- Language
- English
- Date published
- 01/07/2025
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984769722802771
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