Structure of Csx1-cOA4 complex reveals the basis of RNA decay in Type III-B CRISPR-Cas
Rafael Molina,
Stefano Stella,
Mingxia Feng,
Nicholas Sofos,
Vykintas Jauniskis,
Irina Pozdnyakova,
Blanca López-Méndez,
Qunxin She and
Guillermo Montoya ()
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Rafael Molina: Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B
Stefano Stella: Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B
Mingxia Feng: Huazhong Agricultural University
Nicholas Sofos: Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B
Vykintas Jauniskis: Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B
Irina Pozdnyakova: University of Copenhagen, Blegdamsvej 3B
Blanca López-Méndez: University of Copenhagen, Blegdamsvej 3B
Qunxin She: Huazhong Agricultural University
Guillermo Montoya: Faculty of Health and Medical Sciences University of Copenhagen, Blegdamsvej 3-B
Nature Communications, 2019, vol. 10, issue 1, 1-14
Abstract:
Abstract Type III CRISPR-Cas multisubunit complexes cleave ssRNA and ssDNA. These activities promote the generation of cyclic oligoadenylate (cOA), which activates associated CRISPR-Cas RNases from the Csm/Csx families, triggering a massive RNA decay to provide immunity from genetic invaders. Here we present the structure of Sulfolobus islandicus (Sis) Csx1-cOA4 complex revealing the allosteric activation of its RNase activity. SisCsx1 is a hexamer built by a trimer of dimers. Each dimer forms a cOA4 binding site and a ssRNA catalytic pocket. cOA4 undergoes a conformational change upon binding in the second messenger binding site activating ssRNA degradation in the catalytic pockets. Activation is transmitted in an allosteric manner through an intermediate HTH domain, which joins the cOA4 and catalytic sites. The RNase functions in a sequential cooperative fashion, hydrolyzing phosphodiester bonds in 5′-C-C-3′. The degradation of cOA4 by Ring nucleases deactivates SisCsx1, suggesting that this enzyme could be employed in biotechnological applications.
Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12244-z
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DOI: 10.1038/s41467-019-12244-z
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