Cas3

CRISPR-associated protein 3

Thermobifida fusca Cas3 PDB: 4QQW

Identifiers

Symbol

cas3

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Cas3 is an ATP-dependent single-strand DNA (ssDNA) translocase/helicase enzyme that degrades DNA as part of CRISPR based immunity.^[1]

Cas3 is a "signature" protein of class 1 CRISPR systems and functions in a complex known as CASCADE, with other cas genes and a targeting RNA to degrade viral DNA.^[1]

In April 2019 Cornell University researcher Ailong Ke published a paper in the journal Molecular Cell describing a new gene editing CRISPR system, CRISPR-Cas3 which can efficiently delete long swaths of DNA from a targeted site in the human genome. This ability is superior to that achieved with the more common CRISPR-Cas9 systems.^[2]

CONAN, a CRISPR based diagnostic approach was developed utilising Cas3 ^[3]

Structure and function

Thermophile Thermobifida fusca Cas3 is a four domain protein with an N-terminal HD-type nuclease domain, followed by two RecA-like domains forming a superfamily 2 helicase motif, then the Cas3 specific linker and C-terminal domain. Single stranded DNA is passed 3′-to-5′ from the helicase domain to the nuclease domain where it is hydrolysed.^[4]

References

^ ^a ^b He L, St John James M, Radovcic M, Ivancic-Bace I, Bolt EL (February 2020). "Cas3 Protein-A Review of a Multi-Tasking Machine". Genes. 11 (2): 208. doi:10.3390/genes11020208. PMC 7074321. PMID 32085454.
^ "CRISPR-Cas3 innovation holds promise for disease cures, advancing science". Cornell Chronicle. Retrieved 2020-09-07.
^ Yoshimi, Kazuto; Takeshita, Kohei; Yamayoshi, Seiya; Shibumura, Satomi; Yamauchi, Yuko; Yamamoto, Masaki; Yotsuyanagi, Hiroshi; Kawaoka, Yoshihiro; Mashimo, Tomoji (February 2022). "CRISPR-Cas3-based diagnostics for SARS-CoV-2 and influenza virus". iScience. 25 (2): 103830. Bibcode:2022iSci...25j3830Y. doi:10.1016/j.isci.2022.103830. ISSN 2589-0042. PMC 8801231. PMID 35128347.
^ Huo, Yanwu; Nam, Ki Hyun; Ding, Fang; Lee, Heejin; Wu, Lijie; Xiao, Yibei; Farchione, M. Daniel; Zhou, Sharleen; Rajashankar, Kanagalaghatta; Kurinov, Igor; Zhang, Rongguang; Ke, Ailong (2014). "Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA unwinding and degradation". Nature Structural & Molecular Biology. 21 (9): 771–777. doi:10.1038/nsmb.2875. ISSN 1545-9985. PMC 4156918. PMID 25132177.

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