Unexpected molecular diversity of vertebrate nonvisual opsin Opn5

Abstract

Animals depend on light from their external environment to provide information for physiological functions such as vision, photoentrainment of circadian and circannual rhythms, photoperiodism, and background adaptation. Animals have a variety of photoreceptor cells that perform these functions, not only in the retina but also in other tissues, including brain tissue. In these cells, opsins function as universal photoreceptive proteins responsible for both visual and nonvisual photoreception. All opsins identified thus far bind either 11-cis or all-trans retinal as a chromophore and are classified into several groups based on their amino acid sequences. Opn5 forms an independent group that has diversified among vertebrate species. Most mammals only have one Opn5 gene, Opn5m, while nonmammalian vertebrates have two additional Opn5 subtypes, Opn5L1 and Opn5L2. Among these subtypes, Opn5m and Opn5L2 are UV-sensitive pigments in the dark. UV irradiation converts them into the visible light-sensitive active state, which converts back to the dark state by visible light irradiation. Opn5m and Opn5L2 therefore behave as bistable pigments. By contrast, Opn5L1 exclusively binds all-trans retinal to form the active state in the dark. Opn5L1 is converted to the resting state by light irradiation and subsequently reverts to the active state by a thermal process. Thus, Opn5L1 is categorized as a unique reverse photoreceptor whose activity is regulated by its photocyclic reaction. In this review, I introduce the diversity of molecular properties that have been described for vertebrate Opn5 subtypes and their physiological relevance.

Keywords: Opn5; Photoreceptive protein; Retinal; Rhodopsin.

Fig. 1

Comparison of the molecular properties of vertebrate visual rhodopsin (a) and Opn5 (b, c). a Vertebrate visual rhodopsin binds 11-cis retinal exclusively to form the resting state (dark state). Light irradiation converts retinal to the all-trans form, which, in turn, induces the formation of the active state. The resting state cannot be regenerated by irradiating the active state. b In general, Opn5m binds directly to either 11-cis or all-trans retinal to form the resting and active states, respectively. Interconversion between the resting and active state is triggered by light irradiation. Opn5L2 has the molecular property quite similar to Opn5m. c Opn5L1 binds all-trans retinal exclusively to form the active state. Light irradiation causes Opn5L1 to adopt the resting state, and subsequently the active state regenerates via a thermal process

Fig. 2

Molecular phylogenetic classification of vertebrate Opn5 subtypes. Mammals have only one Opn5 gene (Opn5m), whereas nonmammalian vertebrates have Opn5L1 and Opn5L2 genes in addition to Opn5m. The phylogenetic tree was inferred by the maximum-likelihood method after the alignment of amino acid sequences of opsins using ClustalW 2.1 (Larkin et al. 2007). The tree was constructed by MEGA X (Kumar et al. 2018) using JTT matrix-based model (Jones et al. 1992). The numbers at each node are bootstrap probabilities estimated by 1000 replications. Accession numbers of the sequence data in the tree are as follows: human (Homo sapiens) Opn5m, AY377391; mouse (Mus musculus) Opn5m, AY318865; chicken (Gallus gallus) Opn5m, AB368182; Xenopus tropicalis Opn5m, XM_002935990; zebrafish (Danio rerio) Opn5m, AY493740; zebrafish Opn5m2, XM_005157939; spotted gar (Lepisosteus oculatus) Opn5m, XM_015349763; spotted gar Opn5m2, XM_015337843; chicken Opn5L1, AB368181; X. tropicalis Opn5L1a, XM_031904599; X. tropicalis Opn5L1b, NM_001079378; zebrafish Opn5L1a, NM_001316948; zebrafish Opn5L1b, NM_001044992; zebrafish Opn5L1c, NM_001316949; zebrafish Opn5L1d, XM_001340566; spotted gar Opn5L1a, XM_015339535; spotted gar Opn5L1b, XM_015364771; chicken Opn5L2, AB368183; X. tropicalis Opn5L2, XM_004914948; zebrafish Opn5L2a, NM_001316947; zebrafish Opn5L2b, NM_001316945; zebrafish Opn5L2c, NM_001317764; spotted gar Opn5L2a, XM_015343997; spotted gar Opn5L2b, XM_015351606; spotted gar Opn5L2c, XM_015347092; and human Rrh, BC128401.

Fig. 3

Conformational change of Opn5L1-bound retinal to trigger the photocyclic reaction. The dark state binds all-trans retinal to activate G protein. Light irradiation causes retinal isomerization to the 11-cis form to suppress G protein activation. In this state, Cys188 and C11 of retinal form an adduct, thereby converting the double bond of C11=C12 to a single bond. Thermal rotation of the C11–C12 single bond is facile and permits conversion to the all-trans form. In this state, Cys188 and C11 of retinal dissociate to regenerate the original dark state containing all-trans retinal.