Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore

Solano, Yasmeen J.; Everett, Michael P.; Dang, Kelly S.; Abueg, Jude; Kiser, Philip D.

doi:10.1038/s41589-024-01554-z

Title: Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore

Journal Article · 14 February 2024 · Nature Chemical Biology

DOI: https://doi.org/10.1038/s41589-024-01554-z · OSTI ID:2469552

Solano, Yasmeen J. ^[1]; Everett, Michael P. ^[2]; Dang, Kelly S. ^[1]; Abueg, Jude ^[1];

^[2]

University of California, Irvine, CA (United States)
University of California, Irvine, CA (United States); VA Long Beach Healthcare System, Long Beach, CA (United States)

The retinal light response in animals originates from the photoisomerization of an opsin-coupled 11-cis-retinaldehyde chromophore. This visual chromophore is enzymatically produced through the action of carotenoid cleavage dioxygenases. Vertebrates require two carotenoid cleavage dioxygenases, β-carotene oxygenase 1 and retinal pigment epithelium 65 (RPE65), to form 11-cis-retinaldehyde from carotenoid substrates, whereas invertebrates such as insects use a single enzyme known as Neither Inactivation Nor Afterpotential B (NinaB). RPE65 and NinaB couple trans–cis isomerization with hydrolysis and oxygenation, respectively, but the mechanistic relationship of their isomerase activities remains unknown. Here we report the structure of NinaB, revealing details of its active site architecture and mode of membrane binding. Structure-guided mutagenesis studies identify a residue cluster deep within the NinaB substrate-binding cleft that controls its isomerization activity. Our data demonstrate that isomerization activity is mediated by distinct active site regions in NinaB and RPE65—an evolutionary convergence that deepens our understanding of visual system diversity.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); Department of Veterans Affairs; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; AC02-76SF00515

OSTI ID:: 2469552

Journal Information:: Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 6 Vol. 20; ISSN 1552-4450

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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