Scientists have solved the crystal structure of a new protein that can be used for genome editing

Figure from publication (Yamato et al. Crystal Structure of Cpf1 in Complex with Guide RNA and Target DNA. Cell. 2016 May 5;165(4):949-62).

Figure from publication (Yamato et al. Crystal Structure of Cpf1 in Complex with Guide RNA and Target DNA. Cell. 2016 May 5;165(4):949-62).

An international group of scientists have solved the crystal structure of the Cpf1 protein complexed with its DNA-target. This protein is part of a CRISPR system has potential for use in genome editing. Skoltech PhD student Yana Fedorova was one of the authors of this work. Yana studies at the Skoltech Center for Data-Intensive Biomedicine and Biotechnology (DIBB), supervised by Professor Konstantin Severinov. Her work is part of a long-term collaboration between Skoltech DIBB, Eugene Koonin’s lab at the National Institutes of Health (Bethesda, USA) and Feng Zhang’s lab at the Massachusetts Institute of Technology (Boston, USA). Their goal is to systematically search for new CRISPR systems by means of bioinformatics and check the bioinformatic predictions experimentally. Cpf1 and other new CRISPR systems could be used for genome engineering and may have advantages over popular editing tools based on the Cas9 protein.

“The Cpf1 protein is a single effector protein that was found in Acidaminococcus sp. It efficiently creates double-stranded breaks in DNA and has a simpler way of function compared to the classical Cas9 CRISPR effector. Cpf1 can be used for genome editing, activation of gene transcription, or targeting DNA sequences for visualization by microscopy. Making such tools requires understanding of how the protein recognizes and cleaves target DNA. The structural information described in our paper will facilitate the development of a future CRISPR-Cpf1 toolbox”, says Yana Fedorova.

CRISPR-Cas9 technology is revolutionizing the field of genomics. “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are key components of a system used by bacteria to defend against viruses. Cas9 – one of the enzymes produced by the CRISPR system – binds to DNA in a highly sequence-specific manner and cuts it, allowing researchers to target specific regions of the genome and edit them, curing mutations. The new study will serve as a foundation for development of a similar system based on CRISPR-Cpf1.

Results of the work were published in prestigious journal Cell.

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