A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding

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A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding. / Han, Wenyuan; Stella, Stefano; Zhang, Yan; Guo, Tong; Sulek, Karolina; Peng-Lundgren, Li; Montoya, Guillermo; She, Qunxin.

In: Nucleic Acids Research, Vol. 46, No. 19, 2018, p. 10319-10330.

Research output: Contribution to journalJournal article

Harvard

Han, W, Stella, S, Zhang, Y, Guo, T, Sulek, K, Peng-Lundgren, L, Montoya, G & She, Q 2018, 'A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding', Nucleic Acids Research, vol. 46, no. 19, pp. 10319-10330. https://doi.org/10.1093/nar/gky844

APA

Han, W., Stella, S., Zhang, Y., Guo, T., Sulek, K., Peng-Lundgren, L., ... She, Q. (2018). A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding. Nucleic Acids Research, 46(19), 10319-10330. https://doi.org/10.1093/nar/gky844

Vancouver

Han W, Stella S, Zhang Y, Guo T, Sulek K, Peng-Lundgren L et al. A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding. Nucleic Acids Research. 2018;46(19):10319-10330. https://doi.org/10.1093/nar/gky844

Author

Han, Wenyuan ; Stella, Stefano ; Zhang, Yan ; Guo, Tong ; Sulek, Karolina ; Peng-Lundgren, Li ; Montoya, Guillermo ; She, Qunxin. / A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 19. pp. 10319-10330.

Bibtex

@article{f97658447cf64a029bd170b4edc1fa98,
title = "A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding",
abstract = "Recently, Type III-A CRISPR-Cas systems were found to catalyze the synthesis of cyclic oligoadenylates (cOAs), a second messenger that specifically activates Csm6, a Cas accessory RNase and confers antiviral defense in bacteria. To test if III-B CRISPR-Cas systems could mediate a similar CRISPR signaling pathway, the Sulfolobus islandicus Cmr-α ribonucleoprotein complex (Cmr-α-RNP) was purified from the native host and tested for cOA synthesis. We found that the system showed a robust production of cyclic tetra-adenylate (c-A4), and that c-A4 functions as a second messenger to activate the III-B-associated RNase Csx1 by binding to its CRISPR-associated Rossmann Fold domain. Investigation of the kinetics of cOA synthesis revealed that Cmr-α-RNP displayed positively cooperative binding to the adenosine triphosphate (ATP) substrate. Furthermore, mutagenesis of conserved domains in Cmr2α confirmed that, while Palm 2 hosts the active site of cOA synthesis, Palm 1 domain serves as the primary site in the enzyme-substrate interaction. Together, our data suggest that the two Palm domains cooperatively interact with ATP molecules to achieve a robust cOA synthesis by the III-B CRISPR-Cas system.",
author = "Wenyuan Han and Stefano Stella and Yan Zhang and Tong Guo and Karolina Sulek and Li Peng-Lundgren and Guillermo Montoya and Qunxin She",
year = "2018",
doi = "10.1093/nar/gky844",
language = "English",
volume = "46",
pages = "10319--10330",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "19",

}

RIS

TY - JOUR

T1 - A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding

AU - Han, Wenyuan

AU - Stella, Stefano

AU - Zhang, Yan

AU - Guo, Tong

AU - Sulek, Karolina

AU - Peng-Lundgren, Li

AU - Montoya, Guillermo

AU - She, Qunxin

PY - 2018

Y1 - 2018

N2 - Recently, Type III-A CRISPR-Cas systems were found to catalyze the synthesis of cyclic oligoadenylates (cOAs), a second messenger that specifically activates Csm6, a Cas accessory RNase and confers antiviral defense in bacteria. To test if III-B CRISPR-Cas systems could mediate a similar CRISPR signaling pathway, the Sulfolobus islandicus Cmr-α ribonucleoprotein complex (Cmr-α-RNP) was purified from the native host and tested for cOA synthesis. We found that the system showed a robust production of cyclic tetra-adenylate (c-A4), and that c-A4 functions as a second messenger to activate the III-B-associated RNase Csx1 by binding to its CRISPR-associated Rossmann Fold domain. Investigation of the kinetics of cOA synthesis revealed that Cmr-α-RNP displayed positively cooperative binding to the adenosine triphosphate (ATP) substrate. Furthermore, mutagenesis of conserved domains in Cmr2α confirmed that, while Palm 2 hosts the active site of cOA synthesis, Palm 1 domain serves as the primary site in the enzyme-substrate interaction. Together, our data suggest that the two Palm domains cooperatively interact with ATP molecules to achieve a robust cOA synthesis by the III-B CRISPR-Cas system.

AB - Recently, Type III-A CRISPR-Cas systems were found to catalyze the synthesis of cyclic oligoadenylates (cOAs), a second messenger that specifically activates Csm6, a Cas accessory RNase and confers antiviral defense in bacteria. To test if III-B CRISPR-Cas systems could mediate a similar CRISPR signaling pathway, the Sulfolobus islandicus Cmr-α ribonucleoprotein complex (Cmr-α-RNP) was purified from the native host and tested for cOA synthesis. We found that the system showed a robust production of cyclic tetra-adenylate (c-A4), and that c-A4 functions as a second messenger to activate the III-B-associated RNase Csx1 by binding to its CRISPR-associated Rossmann Fold domain. Investigation of the kinetics of cOA synthesis revealed that Cmr-α-RNP displayed positively cooperative binding to the adenosine triphosphate (ATP) substrate. Furthermore, mutagenesis of conserved domains in Cmr2α confirmed that, while Palm 2 hosts the active site of cOA synthesis, Palm 1 domain serves as the primary site in the enzyme-substrate interaction. Together, our data suggest that the two Palm domains cooperatively interact with ATP molecules to achieve a robust cOA synthesis by the III-B CRISPR-Cas system.

U2 - 10.1093/nar/gky844

DO - 10.1093/nar/gky844

M3 - Journal article

C2 - 30239876

VL - 46

SP - 10319

EP - 10330

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 19

ER -

ID: 203050626