Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases

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

Standard

Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases. / Molina, Rafael; Garcia-Martin, Ricardo; López-Méndez, Blanca; Jensen, Anne Louise Grøn; Ciges-Tomas, J. Rafael; Marchena-Hurtado, Javier; Stella, Stefano; Montoya, Guillermo.

In: Nucleic Acids Research, Vol. 50, No. 19, 2022, p. 11199-11213.

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

Harvard

Molina, R, Garcia-Martin, R, López-Méndez, B, Jensen, ALG, Ciges-Tomas, JR, Marchena-Hurtado, J, Stella, S & Montoya, G 2022, 'Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases', Nucleic Acids Research, vol. 50, no. 19, pp. 11199-11213. https://doi.org/10.1093/nar/gkac923

APA

Molina, R., Garcia-Martin, R., López-Méndez, B., Jensen, A. L. G., Ciges-Tomas, J. R., Marchena-Hurtado, J., Stella, S., & Montoya, G. (2022). Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases. Nucleic Acids Research, 50(19), 11199-11213. https://doi.org/10.1093/nar/gkac923

Vancouver

Molina R, Garcia-Martin R, López-Méndez B, Jensen ALG, Ciges-Tomas JR, Marchena-Hurtado J et al. Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases. Nucleic Acids Research. 2022;50(19):11199-11213. https://doi.org/10.1093/nar/gkac923

Author

Molina, Rafael ; Garcia-Martin, Ricardo ; López-Méndez, Blanca ; Jensen, Anne Louise Grøn ; Ciges-Tomas, J. Rafael ; Marchena-Hurtado, Javier ; Stella, Stefano ; Montoya, Guillermo. / Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases. In: Nucleic Acids Research. 2022 ; Vol. 50, No. 19. pp. 11199-11213.

Bibtex

@article{0cd2658997dd46b0b961fbc36899ba9f,
title = "Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases",
abstract = "Standalone ring nucleases are CRISPR ancillary proteins, which downregulate the immune response of Type III CRISPR-Cas systems by cleaving cyclic oligoadenylates (cA) second messengers. Two genes with this function have been found within the Sulfolobus islandicus (Sis) genome. They code for a long polypeptide composed by a CARF domain fused to an HTH domain and a short polypeptide constituted by a CARF domain with a 40 residue C-terminal insertion. Here, we determine the structure of the apo and substrate bound states of the Sis0455 enzyme, revealing an insertion at the C-terminal region of the CARF domain, which plays a key role closing the catalytic site upon substrate binding. Our analysis reveals the key residues of Sis0455 during cleavage and the coupling of the active site closing with their positioning to proceed with cA4 phosphodiester hydrolysis. A time course comparison of cA4 cleavage between the short, Sis0455, and long ring nucleases, Sis0811, shows the slower cleavage kinetics of the former, suggesting that the combination of these two types of enzymes with the same function in a genome could be an evolutionary strategy to regulate the levels of the second messenger in different infection scenarios.",
keywords = "CRISPR-Associated Proteins/metabolism, CRISPR-Cas Systems, Oligoribonucleotides/chemistry, Adenine Nucleotides/metabolism, Endonucleases/metabolism",
author = "Rafael Molina and Ricardo Garcia-Martin and Blanca L{\'o}pez-M{\'e}ndez and Jensen, {Anne Louise Gr{\o}n} and Ciges-Tomas, {J. Rafael} and Javier Marchena-Hurtado and Stefano Stella and Guillermo Montoya",
note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2022",
doi = "10.1093/nar/gkac923",
language = "English",
volume = "50",
pages = "11199--11213",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "19",

}

RIS

TY - JOUR

T1 - Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases

AU - Molina, Rafael

AU - Garcia-Martin, Ricardo

AU - López-Méndez, Blanca

AU - Jensen, Anne Louise Grøn

AU - Ciges-Tomas, J. Rafael

AU - Marchena-Hurtado, Javier

AU - Stella, Stefano

AU - Montoya, Guillermo

N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2022

Y1 - 2022

N2 - Standalone ring nucleases are CRISPR ancillary proteins, which downregulate the immune response of Type III CRISPR-Cas systems by cleaving cyclic oligoadenylates (cA) second messengers. Two genes with this function have been found within the Sulfolobus islandicus (Sis) genome. They code for a long polypeptide composed by a CARF domain fused to an HTH domain and a short polypeptide constituted by a CARF domain with a 40 residue C-terminal insertion. Here, we determine the structure of the apo and substrate bound states of the Sis0455 enzyme, revealing an insertion at the C-terminal region of the CARF domain, which plays a key role closing the catalytic site upon substrate binding. Our analysis reveals the key residues of Sis0455 during cleavage and the coupling of the active site closing with their positioning to proceed with cA4 phosphodiester hydrolysis. A time course comparison of cA4 cleavage between the short, Sis0455, and long ring nucleases, Sis0811, shows the slower cleavage kinetics of the former, suggesting that the combination of these two types of enzymes with the same function in a genome could be an evolutionary strategy to regulate the levels of the second messenger in different infection scenarios.

AB - Standalone ring nucleases are CRISPR ancillary proteins, which downregulate the immune response of Type III CRISPR-Cas systems by cleaving cyclic oligoadenylates (cA) second messengers. Two genes with this function have been found within the Sulfolobus islandicus (Sis) genome. They code for a long polypeptide composed by a CARF domain fused to an HTH domain and a short polypeptide constituted by a CARF domain with a 40 residue C-terminal insertion. Here, we determine the structure of the apo and substrate bound states of the Sis0455 enzyme, revealing an insertion at the C-terminal region of the CARF domain, which plays a key role closing the catalytic site upon substrate binding. Our analysis reveals the key residues of Sis0455 during cleavage and the coupling of the active site closing with their positioning to proceed with cA4 phosphodiester hydrolysis. A time course comparison of cA4 cleavage between the short, Sis0455, and long ring nucleases, Sis0811, shows the slower cleavage kinetics of the former, suggesting that the combination of these two types of enzymes with the same function in a genome could be an evolutionary strategy to regulate the levels of the second messenger in different infection scenarios.

KW - CRISPR-Associated Proteins/metabolism

KW - CRISPR-Cas Systems

KW - Oligoribonucleotides/chemistry

KW - Adenine Nucleotides/metabolism

KW - Endonucleases/metabolism

U2 - 10.1093/nar/gkac923

DO - 10.1093/nar/gkac923

M3 - Journal article

C2 - 36271789

VL - 50

SP - 11199

EP - 11213

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 19

ER -

ID: 325025808