Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins

In addition to core Cas proteins, CRISPR-Cas loci often encode ancillary proteins that modulate the activity of the respective effectors in interference. Subtype VI-B1 CRISPR-Cas systems encode the Csx27 protein that down-regulates the activity of Cas13b when the type VI-B locus is expressed in Esch...

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Main Authors: Makarova, Kira S, Gao, Linyi, Zhang, Feng, Koonin, Eugene V
Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Format: Article
Language:English
Published: Oxford University Press (OUP) 2023
Online Access:https://hdl.handle.net/1721.1/150441
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author Makarova, Kira S
Gao, Linyi
Zhang, Feng
Koonin, Eugene V
author2 Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
author_facet Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Makarova, Kira S
Gao, Linyi
Zhang, Feng
Koonin, Eugene V
author_sort Makarova, Kira S
collection MIT
description In addition to core Cas proteins, CRISPR-Cas loci often encode ancillary proteins that modulate the activity of the respective effectors in interference. Subtype VI-B1 CRISPR-Cas systems encode the Csx27 protein that down-regulates the activity of Cas13b when the type VI-B locus is expressed in Escherichia coli. We show that Csx27 belongs to an expansive family of proteins that contain four predicted transmembrane helices and are typically encoded in predicted operons with components of the bacterial natural transformation machinery, multidomain proteins that consist of components of the ubiquitin signaling system and proteins containing the ligand-binding WYL domain and a helix-turn-helix domain. The Csx27 family proteins are predicted to form membrane channels for ssDNA that might comprise the core of a putative novel, Ub-regulated system for DNA uptake and, possibly, degradation. In addition to these associations, a distinct subfamily of the Csx27 family appears to be a part of a novel, membrane-associated system for DNA modification. In Bacteroidetes, subtype VI-B1 systems might degrade nascent transcripts of foreign DNA in conjunction with its uptake by the bacterial cell. These predictions suggest several experimental directions for the study of type VI CRISPR-Cas systems and distinct mechanisms of foreign DNA uptake and degradation in bacteria.
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spelling mit-1721.1/1504412023-04-07T03:46:26Z Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins Makarova, Kira S Gao, Linyi Zhang, Feng Koonin, Eugene V Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences In addition to core Cas proteins, CRISPR-Cas loci often encode ancillary proteins that modulate the activity of the respective effectors in interference. Subtype VI-B1 CRISPR-Cas systems encode the Csx27 protein that down-regulates the activity of Cas13b when the type VI-B locus is expressed in Escherichia coli. We show that Csx27 belongs to an expansive family of proteins that contain four predicted transmembrane helices and are typically encoded in predicted operons with components of the bacterial natural transformation machinery, multidomain proteins that consist of components of the ubiquitin signaling system and proteins containing the ligand-binding WYL domain and a helix-turn-helix domain. The Csx27 family proteins are predicted to form membrane channels for ssDNA that might comprise the core of a putative novel, Ub-regulated system for DNA uptake and, possibly, degradation. In addition to these associations, a distinct subfamily of the Csx27 family appears to be a part of a novel, membrane-associated system for DNA modification. In Bacteroidetes, subtype VI-B1 systems might degrade nascent transcripts of foreign DNA in conjunction with its uptake by the bacterial cell. These predictions suggest several experimental directions for the study of type VI CRISPR-Cas systems and distinct mechanisms of foreign DNA uptake and degradation in bacteria. 2023-04-06T14:49:32Z 2023-04-06T14:49:32Z 2019 2023-04-06T14:42:01Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150441 Makarova, Kira S, Gao, Linyi, Zhang, Feng and Koonin, Eugene V. 2019. "Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins." FEMS Microbiology Letters, 366 (8). en 10.1093/FEMSLE/FNZ088 FEMS Microbiology Letters This work is written by (a) US Government employee(s) and is in the public domain in the US application/pdf Oxford University Press (OUP) OUP
spellingShingle Makarova, Kira S
Gao, Linyi
Zhang, Feng
Koonin, Eugene V
Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins
title Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins
title_full Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins
title_fullStr Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins
title_full_unstemmed Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins
title_short Unexpected connections between type VI-B CRISPR-Cas systems, bacterial natural competence, ubiquitin signaling network and DNA modification through a distinct family of membrane proteins
title_sort unexpected connections between type vi b crispr cas systems bacterial natural competence ubiquitin signaling network and dna modification through a distinct family of membrane proteins
url https://hdl.handle.net/1721.1/150441
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