Abstract:Heliorhodopsins are enigmatic, novel rhodopsins with a membrane orientation that is opposite to all known rhodopsins. However, their cellular and ecological functions are unknown, and even their taxonomic distribution remains a subject of debate.
“…Bulzu and colleagues identified MORN (Membrane Occupation and Recognition Nexus, PF02493) repeat and zinc ribbon proteins (Pfam domain zinc_ribbon_4) at the N-termini of certain heliorhodopsins; these proteins were modeled to be fused to heliorhodopsins. They suggested that the proteins fused to heliorhodopsins may be related to the PPI or an indication of the role of zinc in possible downstream signaling [ 21 ]. Bulzu and colleagues and Chazan and colleagues also suggested diverse functions resulting from the relationship between heliorhodopsins and neighboring genes.…”
Section: Resultsmentioning
confidence: 99%
“…Heliorhodopsin photocycle was slow, a feature that is widespread in sensory rhodopsins (SRs). Accordingly, Pushkarev and colleagues suggested that heliorhodopsins function as a distinct type of signaling photoreceptors similar to SRs [ 17 ], whereas the N-termini of heliorhodopsins might participate in enzyme function [ 21 ].…”
Photoreceptors are light-sensitive proteins found in various organisms that respond to light and relay signals into the cells. Heliorhodopsin, a retinal-binding membrane protein, has been recently discovered, however its function remains unknown. Herein, we investigated the relationship between Actinobacteria bacterium IMCC26103 heliorhodopsin (AbHeR) and an adjacent glutamine synthetase (AbGS) in the same operon. We demonstrate that AbHeR binds to AbGS and regulates AbGS activity. More specifically, the dissociation constant (Kd) value of the binding between AbHeR and AbGS is 6.06 μM. Moreover, the absence of positively charged residues within the intracellular loop of AbHeR impacted Kd value as they serve as critical binding sites for AbGS. We also confirm that AbHeR up-regulates the biosynthetic enzyme activity of AbGS both in vitro and in vivo in the presence of light. GS is a key enzyme involved in nitrogen assimilation that catalyzes the conversion of glutamate and ammonia to glutamine. Hence, the interaction between AbHeR and AbGS may be critical for nitrogen assimilation in Actinobacteria bacterium IMCC26103 as it survives in low-nutrient environments. Overall, the findings of our study describe, for the first time, to the best of our knowledge, a novel function of heliorhodopsin as a regulatory rhodopsin with the capacity to bind and regulate enzyme activity required for nitrogen assimilation.
“…Bulzu and colleagues identified MORN (Membrane Occupation and Recognition Nexus, PF02493) repeat and zinc ribbon proteins (Pfam domain zinc_ribbon_4) at the N-termini of certain heliorhodopsins; these proteins were modeled to be fused to heliorhodopsins. They suggested that the proteins fused to heliorhodopsins may be related to the PPI or an indication of the role of zinc in possible downstream signaling [ 21 ]. Bulzu and colleagues and Chazan and colleagues also suggested diverse functions resulting from the relationship between heliorhodopsins and neighboring genes.…”
Section: Resultsmentioning
confidence: 99%
“…Heliorhodopsin photocycle was slow, a feature that is widespread in sensory rhodopsins (SRs). Accordingly, Pushkarev and colleagues suggested that heliorhodopsins function as a distinct type of signaling photoreceptors similar to SRs [ 17 ], whereas the N-termini of heliorhodopsins might participate in enzyme function [ 21 ].…”
Photoreceptors are light-sensitive proteins found in various organisms that respond to light and relay signals into the cells. Heliorhodopsin, a retinal-binding membrane protein, has been recently discovered, however its function remains unknown. Herein, we investigated the relationship between Actinobacteria bacterium IMCC26103 heliorhodopsin (AbHeR) and an adjacent glutamine synthetase (AbGS) in the same operon. We demonstrate that AbHeR binds to AbGS and regulates AbGS activity. More specifically, the dissociation constant (Kd) value of the binding between AbHeR and AbGS is 6.06 μM. Moreover, the absence of positively charged residues within the intracellular loop of AbHeR impacted Kd value as they serve as critical binding sites for AbGS. We also confirm that AbHeR up-regulates the biosynthetic enzyme activity of AbGS both in vitro and in vivo in the presence of light. GS is a key enzyme involved in nitrogen assimilation that catalyzes the conversion of glutamate and ammonia to glutamine. Hence, the interaction between AbHeR and AbGS may be critical for nitrogen assimilation in Actinobacteria bacterium IMCC26103 as it survives in low-nutrient environments. Overall, the findings of our study describe, for the first time, to the best of our knowledge, a novel function of heliorhodopsin as a regulatory rhodopsin with the capacity to bind and regulate enzyme activity required for nitrogen assimilation.
“…This fosmid had low sequence similarity to known rhodopsins, which attributed to the lack of detection of HeRs in typical bioinformatic searches 1 . Now, 22 more HeRs have been discovered through pigmented E. coli screens 3 , 4 , and over 400 unique HeR sequences have been found from homology searches of whole genomes from microorganisms 5 , 6 . It turns out that HeRs comprise a large and diverse group of rhodopsins.…”
mentioning
confidence: 99%
“…Moreover, HeRs can be found in psychrophiles, mesophiles, and hyperthermophiles that live in various temperature environments 1 , 8 . Interestingly, bioinformatic analysis revealed that HeRs are found in gram positive bacteria and are largely absent in gram negative bacteria 6 , 8 , although this taxonomic distribution in monoderms and diderms was somewhat debated 5 . Figure 1 Phylogenetic tree of microbial rhodopsins with representative HeRs and type I rhodopsins.…”
mentioning
confidence: 99%
“…If HeRs are indeed sensors, the transducer proteins have not yet been identified, because HeRs lack a consistent set of gene neighbours 4 . A wide genomic and metagenomic search provided compelling evidence that some HeRs are linked to histidine kinases, while other HeRs may be N-terminally fused to a MORN-repeat (Membrane Occupation and Recognition Nexus) or a Zinc-finger functional domain 6 . Another analysis of HeR-coding DNA segments revealed two protein families that were unique gene neighbors among some HeRs: Blh (β-carotene 15,15′-dioxygenase), required for the last step in the retinal biosynthetic pathway in prokaryotes; and the DegV family involved in activating fatty acids 4 .…”
Within the microbial rhodopsin family, heliorhodopsins (HeRs) form a phylogenetically distinct group of light-harvesting retinal proteins with largely unknown functions. We have determined the 1.97 Å resolution X-ray crystal structure of Thermoplasmatales archaeon SG8-52-1 heliorhodopsin (TaHeR) in the presence of NaCl under acidic conditions (pH 4.5), which complements the known 2.4 Å TaHeR structure acquired at pH 8.0. The low pH structure revealed that the hydrophilic Schiff base cavity (SBC) accommodates a chloride anion to stabilize the protonated retinal Schiff base when its primary counterion (Glu-108) is neutralized. Comparison of the two structures at different pH revealed conformational changes connecting the SBC and the extracellular loop linking helices A–B. We corroborated this intramolecular signaling transduction pathway with computational studies, which revealed allosteric network changes propagating from the perturbed SBC to the intracellular and extracellular space, suggesting TaHeR may function as a sensory rhodopsin. This intramolecular signaling mechanism may be conserved among HeRs, as similar changes were observed for HeR 48C12 between its pH 8.8 and pH 4.3 structures. We additionally performed DEER experiments, which suggests that TaHeR forms possible dimer-of-dimer associations which may be integral to its putative functionality as a light sensor in binding a transducer protein.
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