Protein Modeling/CRISPR-Cas9

The CRISPR-Cas9 and Anti-CRISPR proteins are the topic of Protein Modeling for the 2018-2019 season. The CRISPR complex known as Cascade can be found under the Protein Data Bank ID 4QYZ, and the Cas9 protein can be found under the ID 4OO8. The pre-build model is the anti-CRISPR protein AcrII4A, which can be found under the ID 5XN4.

Function
CRISPR stands for clustered regularly interspaced short palindromic repeats, and it refers to a family of DNA sequences found in prokaryotes that defend the organism from bacteriophages. The Cas9 (CRISPR associated 9) enzymes use CRISPR to cut specific DNA strands complementary to the CRISPR sequence. In prokaryotic organisms with CRISPR genes, the Cas9 enzymes cut viral DNA so the organism does not get infected by it. When used with CRISPR sequences in other organisms, Cas9 enzymes can be used to edit the genes of different organisms. RNA guided Cas proteins can also be used to cut RNA strands. CRISPR sequences are found in approximately 50% of bacteria and 90% of archaea that have been sequenced.

Anti-CRISPR can be used by phages to deactivate the CRISPR system, protecting viruses from having their DNA destroyed. These proteins mimic DNA so that the Cas9 protein binds to them, preventing it from cutting the real DNA. The anti-CRISPR proteins target specific spots on Cas9 so that it cannot function after the proteins bind to it. This also means that once a gene is edited with CRISPR-Cas9 technology, the process can be stopped so that no parts of an organism's DNA are harmed by the system.

Protospacer adjacent motifs (PAM) are also important in the function of anti-CRISPR proteins. CRISPR proteins will not cut DNA if it is not followed immediately by the PAM sequence in an invading virus. In genetic editing, this requirement can be used to target specific mutations without affecting other alleles.

Structure
The Cas9 protein has a bi-lobed structure.

Resources

 * Cas9 on Wikipedia
 * The official Center for BioMolecular Modeling page on the Protein Modeling event
 * Protein Modeling SciOly.org Wiki