9ZS2

S. marcescens Cas10-Csm unbound to target RNA

This is a non-PDB format compatible entry.

Summary for 9ZS2

• Entry DOI: 10.2210/pdb9zs2/pdb
• EMDB information: 74675
• Descriptor: CRISPR system single-strand-specific deoxyribonuclease Cas10/Csm1 (subtype III-A), CRISPR system Cms endoribonuclease Csm3, CRISPR system Cms protein Csm4, ... (5 entities in total)
• Functional Keywords: crispr, crrna, cas10, type iii, rna binding protein
• Biological source: Serratia; More
• Total number of polymer chains: 8
• Total formula weight: 311415.30

Authors

Perdigao, C.C.,Dokland, T.,Dunkle, J.A. (deposition date: 2025-12-22, release date: 2026-04-22)

Primary citation

Perdigao, C.C.,Ajisafe, L.O.,Sunny, A.T.,Wu, S.,Dokland, T.,Dunkle, J.A.
Structural insights into target detection by the S. marcescens type III CRISPR complex and its deployment in SNP identification.
Biorxiv, 2026

PubMed Abstract: Type III CRISPR systems utilize a complex containing Cas10, additional Cas proteins and a crRNA to detect foreign transcripts. Upon detection, Cas10 synthesizes cyclic oligoadenylates (cOA), signaling molecules that coordinate interference by stimulating downstream enzymes with DNase, RNase, protease or other activities. Type III systems are among the most abundant CRISPR systems in prokaryotes and understanding the structure-function relationships that control transcript detection and cOA synthesis will advance the understanding of the broader physiological roles of these systems. Type III systems possess properties well-suited to their deployment as molecule diagnostics: specific detection and activation of a cascade of multi-turnover enzymatic reactions that can be harnessed for signal generation. We determined that Cas10-Csm (SmCas10-Csm) synthesizes predominantly cA molecules and this synthesis is sensitive to mismatches in the crRNA-target RNA duplex adjacent to Cas10. We determined the structure of SmCas10-Csm unbound and bound to target RNA identifying conformational changes associated with target binding. We demonstrate that SmCas10-Csm can distinguish between single nucleotide polymorphisms that occur in the human transcript that are associated with sickle cell disease indicating an additional role for type III CRISPR systems in point-of-care diagnostics in low-resource settings.

PubMed: 41959359
DOI: 10.64898/2026.03.30.715313

Experimental method

ELECTRON MICROSCOPY (4.4 Å)