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      A Large and Phylogenetically Diverse Class of Type 1 Opsins Lacking a Canonical Retinal Binding Site

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          Abstract

          Opsins are photosensitive proteins catalyzing light-dependent processes across the tree of life. For both microbial (type 1) and metazoan (type 2) opsins, photosensing depends upon covalent interaction between a retinal chromophore and a conserved lysine residue. Despite recent discoveries of potential opsin homologs lacking this residue, phylogenetic dispersal and functional significance of these abnormal sequences have not yet been investigated. We report discovery of a large group of putatively non-retinal binding opsins, present in a number of fungal and microbial genomes and comprising nearly 30% of opsins in the Halobacteriacea, a model clade for opsin photobiology. We report phylogenetic analyses, structural modeling, genomic context analysis and biochemistry, to describe the evolutionary relationship of these recently described proteins with other opsins, show that they are expressed and do not bind retinal in a canonical manner. Given these data, we propose a hypothesis that these abnormal opsin homologs may represent a novel family of sensory opsins which may be involved in taxis response to one or more non-light stimuli. If true, this finding would challenge our current understanding of microbial opsins as a light-specific sensory family, and provides a potential analogy with the highly diverse signaling capabilities of the eukaryotic G-protein coupled receptors (GPCRs), of which metazoan type 2 opsins are a light-specific sub-clade.

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          Most cited references31

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          MRBAYES: Bayesian inference of phylogenetic trees.

          The program MRBAYES performs Bayesian inference of phylogeny using a variant of Markov chain Monte Carlo. MRBAYES, including the source code, documentation, sample data files, and an executable, is available at http://brahms.biology.rochester.edu/software.html.
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            Protein structure prediction using Rosetta.

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              Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex.

              The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 June 2016
                2016
                : 11
                : 6
                : e0156543
                Affiliations
                [1 ]Genome Center, One Shields Ave., University of California Davis, Davis, CA, 95616, United States of America
                [2 ]Microbiology Graduate Group, One Shields Ave., University of California Davis, Davis, CA, 95616, United States of America
                [3 ]Department of Biomedical Engineering, One Shields Ave., University of California Davis, Davis, CA, 95616, United States of America
                [4 ]Proteome Software, 1340 SW Bertha Blvd., Portland, Oregon, United States of America
                [5 ]California Department of Food and Agriculture, 1220 N St., Sacramento, CA, 95814, United States of America
                [6 ]William’s College, 880 Main St., Williamstown, MA, 01267, United States of America
                [7 ]Department of Physiology and Membrane Biology, One Shields Ave., University of California Davis, Davis, CA, 95616, United States of America
                Max F. Perutz Laboratories, AUSTRIA
                Author notes

                Competing Interests: PMS is currently an employee of Proteome Software, Portland, Oregon, USA. However, this employment began after completion of work on this manuscript. The authors declare that no competing interests exist. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: EAB MTF. Performed the experiments: EAB AIY PMS TK TW RE VY. Analyzed the data: EAB AIY MTF PMS TK KSYS VY. Contributed reagents/materials/analysis tools: MTF RE TK VY. Wrote the paper: EAB MTF VY TK AIY RE PMS.

                Article
                PONE-D-16-11946
                10.1371/journal.pone.0156543
                4915679
                27327432
                dc40e7ab-7e69-4a76-b378-f4c78df99953
                © 2016 Becker et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 March 2016
                : 19 April 2016
                Page count
                Figures: 4, Tables: 0, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000156, Division of Emerging Frontiers;
                Award ID: EF0949453
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007707, University of California, Davis;
                Award ID: Bridge Funds
                Award Recipient :
                Funding for this work came from the National Science Foundation [EF0949453] and departmental and bridge funds to MTF. The funder provided support in the form of salaries for author PMS, AIY, EAB and MTF but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
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                Research and Analysis Methods
                Database and Informatics Methods
                Biological Databases
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                Molecular Biology
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                Sequence Analysis
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                Biology and Life Sciences
                Molecular Biology
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                Phylogenetic Analysis
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                Custom metadata
                Haloarchaeal genomes can be accessed through the NCBI Genomes database under the following accession numbers: AOHS-AOIE, AOII-AOIW, AOJD-AOJO, AOLD-AOLS, AOLW-AOMF. Some supplemental data are available at DataDryad with accession number ( http://dx.doi.org/10.5061/dryad.963hr).

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