Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases. / Molina Monterrubio, Rafael Arcangel; Jensen, Anne Louise Grøn; Marchena-Hurtado, Javier; López-Méndez, Blanca; Stella, Stefano; Montoya, Guillermo.

In: Nucleic Acids Research, Vol. 49, No. 21, 2021, p. 12577-12590.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Molina Monterrubio, RA, Jensen, ALG, Marchena-Hurtado, J, López-Méndez, B, Stella, S & Montoya, G 2021, 'Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases', Nucleic Acids Research, vol. 49, no. 21, pp. 12577-12590. https://doi.org/10.1093/nar/gkab1130

APA

Molina Monterrubio, R. A., Jensen, A. L. G., Marchena-Hurtado, J., López-Méndez, B., Stella, S., & Montoya, G. (2021). Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases. Nucleic Acids Research, 49(21), 12577-12590. https://doi.org/10.1093/nar/gkab1130

Vancouver

Molina Monterrubio RA, Jensen ALG, Marchena-Hurtado J, López-Méndez B, Stella S, Montoya G. Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases. Nucleic Acids Research. 2021;49(21):12577-12590. https://doi.org/10.1093/nar/gkab1130

Author

Molina Monterrubio, Rafael Arcangel ; Jensen, Anne Louise Grøn ; Marchena-Hurtado, Javier ; López-Méndez, Blanca ; Stella, Stefano ; Montoya, Guillermo. / Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases. In: Nucleic Acids Research. 2021 ; Vol. 49, No. 21. pp. 12577-12590.

Bibtex

@article{01c0556562bc417b8896e6b85ab00afe,
title = "Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases",
abstract = "Type III CRISPR-Cas effector systems detect foreign RNA triggering DNA and RNA cleavage and synthesizing cyclic oligoadenylate molecules (cA) in their Cas10 subunit. cAs act as a second messenger activating auxiliary nucleases, leading to an indiscriminate RNA degradation that can end in cell dormancy or death. Standalone ring nucleases are CRISPR ancillary proteins which downregulate the strong immune response of Type III systems by degrading cA. These enzymes contain a CRISPR-associated Rossman-fold (CARF) domain, which binds and cleaves the cA molecule. Here, we present the structures of the standalone ring nuclease from Sulfolobus islandicus (Sis) 0811 in its apo and post-catalytic states. This enzyme is composed by a N-terminal CARF and a C-terminal wHTH domain. Sis0811 presents a phosphodiester hydrolysis metal-independent mechanism, which cleaves cA4 rings to generate linear adenylate species, thus reducing the levels of the second messenger and switching off the cell antiviral state. The structural and biochemical analysis revealed the coupling of a cork-screw conformational change with the positioning of key catalytic residues to proceed with cA4 phosphodiester hydrolysis in a non-concerted manner.",
author = "{Molina Monterrubio}, {Rafael Arcangel} and Jensen, {Anne Louise Gr{\o}n} and Javier Marchena-Hurtado and Blanca L{\'o}pez-M{\'e}ndez and Stefano Stella and Guillermo Montoya",
year = "2021",
doi = "10.1093/nar/gkab1130",
language = "English",
volume = "49",
pages = "12577--12590",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "21",

}

RIS

TY - JOUR

T1 - Structural basis of cyclic oligoadenylate degradation by ancillary Type III CRISPR-Cas ring nucleases

AU - Molina Monterrubio, Rafael Arcangel

AU - Jensen, Anne Louise Grøn

AU - Marchena-Hurtado, Javier

AU - López-Méndez, Blanca

AU - Stella, Stefano

AU - Montoya, Guillermo

PY - 2021

Y1 - 2021

N2 - Type III CRISPR-Cas effector systems detect foreign RNA triggering DNA and RNA cleavage and synthesizing cyclic oligoadenylate molecules (cA) in their Cas10 subunit. cAs act as a second messenger activating auxiliary nucleases, leading to an indiscriminate RNA degradation that can end in cell dormancy or death. Standalone ring nucleases are CRISPR ancillary proteins which downregulate the strong immune response of Type III systems by degrading cA. These enzymes contain a CRISPR-associated Rossman-fold (CARF) domain, which binds and cleaves the cA molecule. Here, we present the structures of the standalone ring nuclease from Sulfolobus islandicus (Sis) 0811 in its apo and post-catalytic states. This enzyme is composed by a N-terminal CARF and a C-terminal wHTH domain. Sis0811 presents a phosphodiester hydrolysis metal-independent mechanism, which cleaves cA4 rings to generate linear adenylate species, thus reducing the levels of the second messenger and switching off the cell antiviral state. The structural and biochemical analysis revealed the coupling of a cork-screw conformational change with the positioning of key catalytic residues to proceed with cA4 phosphodiester hydrolysis in a non-concerted manner.

AB - Type III CRISPR-Cas effector systems detect foreign RNA triggering DNA and RNA cleavage and synthesizing cyclic oligoadenylate molecules (cA) in their Cas10 subunit. cAs act as a second messenger activating auxiliary nucleases, leading to an indiscriminate RNA degradation that can end in cell dormancy or death. Standalone ring nucleases are CRISPR ancillary proteins which downregulate the strong immune response of Type III systems by degrading cA. These enzymes contain a CRISPR-associated Rossman-fold (CARF) domain, which binds and cleaves the cA molecule. Here, we present the structures of the standalone ring nuclease from Sulfolobus islandicus (Sis) 0811 in its apo and post-catalytic states. This enzyme is composed by a N-terminal CARF and a C-terminal wHTH domain. Sis0811 presents a phosphodiester hydrolysis metal-independent mechanism, which cleaves cA4 rings to generate linear adenylate species, thus reducing the levels of the second messenger and switching off the cell antiviral state. The structural and biochemical analysis revealed the coupling of a cork-screw conformational change with the positioning of key catalytic residues to proceed with cA4 phosphodiester hydrolysis in a non-concerted manner.

U2 - 10.1093/nar/gkab1130

DO - 10.1093/nar/gkab1130

M3 - Journal article

C2 - 34850143

VL - 49

SP - 12577

EP - 12590

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 21

ER -

ID: 286698914