9CXI

Structure of PDE6C in complex with the rod inhibitory p gamma subunit in the absence of added cGMP

Summary for 9CXI

• Entry DOI: 10.2210/pdb9cxi/pdb
• EMDB information: 45992
• Descriptor: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha', rod pg, ZINC ION, ... (5 entities in total)
• Functional Keywords: pde6-cgmp-gmp complex, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 218430.51

Authors

Srivastava, D.,Singh, S.,Artemyev, N. (deposition date: 2024-07-31, release date: 2024-12-18, Last modification date: 2025-05-14)

Primary citation

Singh, S.,Srivastava, D.,Boyd, K.,Artemyev, N.O.
Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision.
Proc.Natl.Acad.Sci.USA, 122:e2419732121-e2419732121, 2025

PubMed 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.

PubMed: 39739818
DOI: 10.1073/pnas.2419732121

Experimental method

ELECTRON MICROSCOPY (3 Å)