11HC

Effector complex from type IV-C CRISPR-Cas system

Summary for 11HC

• Entry DOI: 10.2210/pdb11hc/pdb
• EMDB information: 75685
• Descriptor: Cas10IVc, Cas5c, Cas7c, ... (8 entities in total)
• Functional Keywords: crispr-cas, nuclease, rna-guided, cas10, cas7, rna binding protein
• Biological source: Pyrococcus abyssi; More
• Total number of polymer chains: 17
• Total formula weight: 470270.77

Authors

Pittman, C.,Xu, C.,Catchpole, R.,Garrett, S.,Fuchs, R.,Makarova, K.,Koonin, E.,Zhao, P.,Wells, L.,Graveley, B.,Chu, X.,Ke, A.,Terns, M. (deposition date: 2026-02-23, release date: 2026-08-26, Last modification date: 2026-09-16)

Primary citation

Pittman, C.C.,Xu, C.,Catchpole, R.J.,Garrett, S.,Fuchs, R.,Chu, X.,Makarova, K.S.,Koonin, E.V.,Zhao, P.,Wells, L.,Graveley, B.R.,Ke, A.,Terns, M.P.
Type IV-C CRISPR-Cas effector complexes recognize double-stranded DNA and switch on collateral cleavage of ssDNA and RNA.
Cell Rep, 45:117939-117939, 2026

PubMed Abstract: Type IV-C CRISPR-Cas systems remain enigmatic compared to other class 1 systems. Here, we expand the type IV-C catalog, identifying two phylogenetically distinct clades primarily found in archaea (IV-C1) or bacteria (IV-C2), distinguishable by the Cas10IVc subunit architecture. We functionally and structurally characterize type IV-C1 systems from Thermococcus onnurineus (Ton) and Pyrococcus abyssi (Pab). Type IV-C complexes assemble with crRNAs derived from distinct CRISPR arrays and recognize a 5'-GGG-3' protospacer adjacent motif (PAM) to bind double-stranded DNA targets. Target recognition activates the HD domain of Cas10IVc, triggering metal-dependent collateral cleavage of single-stranded DNA and RNA. This behavior is explained by allosteric alignment of the HD active site, triggered by PAM-dependent R-loop formation, as revealed by cryo-EM. Together, our findings suggest that type IV-C systems provide immunity via non-specific cleavage of nucleic acids generated during mobile genetic element replication or transcription.

PubMed: 42700392
DOI: 10.1016/j.celrep.2026.117939

Experimental method

ELECTRON MICROSCOPY (3.37 Å)