Photoglobin, a distinct family of non-heme binding globins, defines a potential photosensor in prokaryotic signal transduction systems

Globins constitute an ancient superfamily of proteins, exhibiting enormous structural and functional diversity, as demonstrated by many heme-binding families and two non-heme binding families that were discovered in bacterial stressosome component RsbR and in light-harvesting phycobiliproteins (phycocyanin) in cyanobacteria and red algae. By comprehensively exploring the globin repertoire using sensitive computational analyses of sequences, structures, and genomes, we present the identification of the third family of non-heme binding globins-the photoglobin. By conducting profile-based comparisons, clustering analyses, and structural modeling, we demonstrate that photoglobin is related to, but distinct from, the phycocyanin family. Photoglobin preserves a potential ligand-binding pocket, whose residue configuration closely resembles that of phycocyanin, indicating that photoglobin potentially binds to a comparable linear tetrapyrrole. By exploring the contextual information provided by the photoglobin's domain architectures and gene-neighborhoods, we found that photoglobin is frequently associated with the B12-binding light sensor domain and many domains typical of prokaryotic signal transduction systems. Structural modeling using AlphaFold2 demonstrated that photoglobin and B12-binding domains form a structurally conserved hub among different domain architecture contexts. Based on these strong associations, we predict that the coupled photoglobin and B12-binding domains act as a light-sensing regulatory bundle, with each domain sensing different wavelengths of light resulting in switch-like regulation of downstream signaling effectors. Thus, based on the above lines of evidence, we present a distinct non-heme binding globin family and propose that it may define a new type of light sensor, by means of a linear tetrapyrrole, in complex prokaryotic signal transduction systems.(c) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

By conducting computational analyses, the authors identified a new type of non-heme binding globin called photoglobin, which may act as a light sensor in complex prokaryotic signal transduction systems.