6R7B

Crystal structure of Csx1 in complex with cyclic oligoadenylate cOA4 conformation 1

Summary for 6R7B

• Entry DOI: 10.2210/pdb6r7b/pdb
• Related: 6QZQ 6QZT
• EMDB information: 4691
• Descriptor: CRISPR-associated (Cas) DxTHG family, RNA (5'-R(P*AP*AP*AP*A)-3') (3 entities in total)
• Functional Keywords: crispr associated protein carf hepn rnase, rna binding protein
• Biological source: Sulfolobus islandicus; More
• Total number of polymer chains: 5
• Total formula weight: 158121.92

Authors

Molina, R.,Montoya, G.,Sofos, N.,Stella, S. (deposition date: 2019-03-28, release date: 2019-10-02, Last modification date: 2024-10-16)

Primary citation

Molina, R.,Stella, S.,Feng, M.,Sofos, N.,Jauniskis, V.,Pozdnyakova, I.,Lopez-Mendez, B.,She, Q.,Montoya, G.
Structure of Csx1-cOA4complex reveals the basis of RNA decay in Type III-B CRISPR-Cas.
Nat Commun, 10:4302-4302, 2019

PubMed 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-cOA complex revealing the allosteric activation of its RNase activity. SisCsx1 is a hexamer built by a trimer of dimers. Each dimer forms a cOA binding site and a ssRNA catalytic pocket. cOA 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 cOA and catalytic sites. The RNase functions in a sequential cooperative fashion, hydrolyzing phosphodiester bonds in 5'-C-C-3'. The degradation of cOA by Ring nucleases deactivates SisCsx1, suggesting that this enzyme could be employed in biotechnological applications.

PubMed: 31541109
DOI: 10.1038/s41467-019-12244-z

Experimental method

X-RAY DIFFRACTION (3.12 Å)