10vb

Crystal structure of GeoCas9 HNH domain bound to S78A mutant anti-CRISPR AcrIIC1

spinqualitylabelsall models 10vb, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 10vb is a 12 chain structure with sequence from Geobacillus stearothermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Anti-CRISPRs (Acrs) are small protein inhibitors of CRISPR-Cas effectors that originate from the translated genetic material of bacteriophage. Harnessing the natural ability of Acrs to bind and disrupt CRISPR-Cas editing can provide enhanced spatiotemporal control of gene editing. Recent studies have revealed diverse structures and functions of Acrs, however, atomistic studies of the specific molecular mechanisms behind Acr inhibition are lacking. Here, we reveal how structure, function, and dynamics govern AcrIIC1 inhibition of Cas9 from G. stearothermophilus ( Geo Cas9) via its HNH nuclease domain. An X-ray crystal structure of the Geo HNH-AcrIIC1complex reveals a conserved binding interface at the catalytic site and disruption of crucial electrostatic contacts known to modulate the thermostability of Geo Cas9. AcrIIC1 binding also rewires the intrinsic dynamics of the Geo HNH domain, stimulates millisecond motions that are absent from the unliganded nuclease, and attenuates the guide RNA affinity of Geo Cas9. Subsequent AcrIIC1 mutations in residues at its crystallographic binding interface uncouple Acr binding from inhibition, providing new insight into mechanism by which AcrIIC1 acts on Geo Cas9. Orthosteric and allosteric effects of anti-CRISPR II-C1 inhibition on Geo Cas9 from integrated structural biophysics.,Knight AL, Belato HB, Dresser CS, Pindi C, Mercado BJ, Lasekan P, Luo J, Arantes PR, Jogl G, Palermo G, Lisi GP bioRxiv [Preprint]. 2026 Apr 9:2026.04.08.717222. doi: , 10.64898/2026.04.08.717222. PMID:41993526 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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