Heliorhodopsin-mediated Light-modulation of ABC Transporter

Overview

Journal Nat Commun

Specialty Biology

Date 2024 May 21

PMID 38773114

Authors

Shin-Gyu Cho

Ji-Hyun Kim

Ji-Eun Lee

In-Jung Choi

Myungchul Song

Kimleng Chuon

Jin-Gon Shim

Kun-Wook Kang

Kwang-Hwan Jung

Affiliations

Soon will be listed here.

Abstract

Heliorhodopsins (HeRs) have been hypothesized to have widespread functions. Recently, the functions for few HeRs have been revealed; however, the hypothetical functions remain largely unknown. Herein, we investigate light-modulation of heterodimeric multidrug resistance ATP-binding cassette transporters (OmrDE) mediated by Omithinimicrobium cerasi HeR. In this study, we classifiy genes flanking the HeR-encoding genes and identify highly conservative residues for protein-protein interactions. Our results reveal that the interaction between OcHeR and OmrDE shows positive cooperatively sequential binding through thermodynamic parameters. Moreover, light-induced OcHeR upregulates OmrDE drug transportation. Hence, the binding may be crucial to drug resistance in O. cerasi as it survives in a drug-containing habitat. Overall, we unveil a function of HeR as regulatory rhodopsin for multidrug resistance. Our findings suggest potential applications in optogenetic technology.

References

Spudich J, Yang C, Jung K, Spudich E . Retinylidene proteins: structures and functions from archaea to humans. Annu Rev Cell Dev Biol. 2000; 16:365-92. DOI: 10.1146/annurev.cellbio.16.1.365. View

Rozenberg A, Inoue K, Kandori H, Beja O . Microbial Rhodopsins: The Last Two Decades. Annu Rev Microbiol. 2021; 75:427-447. DOI: 10.1146/annurev-micro-031721-020452. View

Ernst O, Lodowski D, Elstner M, Hegemann P, Brown L, Kandori H . Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem Rev. 2013; 114(1):126-63. PMC: 3979449. DOI: 10.1021/cr4003769. View

Finkel O, Beja O, Belkin S . Global abundance of microbial rhodopsins. ISME J. 2012; 7(2):448-51. PMC: 3554412. DOI: 10.1038/ismej.2012.112. View

Gomez-Consarnau L, Raven J, Levine N, Cutter L, Wang D, Seegers B . Microbial rhodopsins are major contributors to the solar energy captured in the sea. Sci Adv. 2019; 5(8):eaaw8855. PMC: 6685716. DOI: 10.1126/sciadv.aaw8855. View

Pushkarev A, Inoue K, Larom S, Flores-Uribe J, Singh M, Konno M . A distinct abundant group of microbial rhodopsins discovered using functional metagenomics. Nature. 2018; 558(7711):595-599. PMC: 11128463. DOI: 10.1038/s41586-018-0225-9. View

Shihoya W, Inoue K, Singh M, Konno M, Hososhima S, Yamashita K . Crystal structure of heliorhodopsin. Nature. 2019; 574(7776):132-136. DOI: 10.1038/s41586-019-1604-6. View

Kovalev K, Volkov D, Astashkin R, Alekseev A, Gushchin I, Haro-Moreno J . High-resolution structural insights into the heliorhodopsin family. Proc Natl Acad Sci U S A. 2020; 117(8):4131-4141. PMC: 7049168. DOI: 10.1073/pnas.1915888117. View

Jung K . The distinct signaling mechanisms of microbial sensory rhodopsins in Archaea, Eubacteria and Eukarya. Photochem Photobiol. 2006; 83(1):63-9. DOI: 10.1562/2006-03-20-IR-853. View

10.

Chazan A, Rozenberg A, Mannen K, Nagata T, Tahan R, Yaish S . Diverse heliorhodopsins detected via functional metagenomics in freshwater Actinobacteria, Chloroflexi and Archaea. Environ Microbiol. 2022; 24(1):110-121. DOI: 10.1111/1462-2920.15890. View

11.

Cho S, Song M, Chuon K, Shim J, Meas S, Jung K . Heliorhodopsin binds and regulates glutamine synthetase activity. PLoS Biol. 2022; 20(10):e3001817. PMC: 9529153. DOI: 10.1371/journal.pbio.3001817. View

12.

Shim J, Cho S, Kim S, Chuon K, Meas S, Choi A . Heliorhodopsin Helps Photolyase to Enhance the DNA Repair Capacity. Microbiol Spectr. 2022; 10(6):e0221522. PMC: 9769723. DOI: 10.1128/spectrum.02215-22. View

13.

Hososhima S, Mizutori R, Abe-Yoshizumi R, Rozenberg A, Shigemura S, Pushkarev A . Proton-transporting heliorhodopsins from marine giant viruses. Elife. 2022; 11. PMC: 9448325. DOI: 10.7554/eLife.78416. View

14.

Locher K . Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat Struct Mol Biol. 2016; 23(6):487-93. DOI: 10.1038/nsmb.3216. View

15.

Rech S, Deppenmeier U, Gunsalus R . Regulation of the molybdate transport operon, modABCD, of Escherichia coli in response to molybdate availability. J Bacteriol. 1995; 177(4):1023-9. PMC: 176698. DOI: 10.1128/jb.177.4.1023-1029.1995. View

16.

de Veaux L, Clevenson D, Bradbeer C, Kadner R . Identification of the btuCED polypeptides and evidence for their role in vitamin B12 transport in Escherichia coli. J Bacteriol. 1986; 167(3):920-7. PMC: 215959. DOI: 10.1128/jb.167.3.920-927.1986. View

17.

Rodionov D, Hebbeln P, Eudes A, Ter Beek J, Rodionova I, Erkens G . A novel class of modular transporters for vitamins in prokaryotes. J Bacteriol. 2008; 191(1):42-51. PMC: 2612444. DOI: 10.1128/JB.01208-08. View

18.

Lubelski J, de Jong A, van Merkerk R, Agustiandari H, Kuipers O, Kok J . LmrCD is a major multidrug resistance transporter in Lactococcus lactis. Mol Microbiol. 2006; 61(3):771-81. DOI: 10.1111/j.1365-2958.2006.05267.x. View

19.

Zutz A, Hoffmann J, Hellmich U, Glaubitz C, Ludwig B, Brutschy B . Asymmetric ATP hydrolysis cycle of the heterodimeric multidrug ABC transport complex TmrAB from Thermus thermophilus. J Biol Chem. 2010; 286(9):7104-15. PMC: 3044967. DOI: 10.1074/jbc.M110.201178. View

20.

Nishino K, Yamaguchi A . Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol. 2001; 183(20):5803-12. PMC: 99656. DOI: 10.1128/JB.183.20.5803-5812.2001. View