The type III CRISPR-Cas system resists the molecular mechanism of exogenous nucleic acids.

On November 29th, Cell magazine published an online research paper on "Structure Studies of the INSTITUTE of Biophysics of the Chinese Academy of Sciences, " Structure of the CRISPR-Csm Complex Reveal Mechanism of Co-co-directoral Lyonal Cell", in collaboration with the Zhang New Deal Task Force.
the work analyzed the structure of Csm of the III-A CRISPR-Cas system effect complex in different states, and combined with the functional experiments in vivo and in vitro, systematically expounded the molecular mechanism of the TYPE III CRISPR-Cas system to resist the exogenous nucleic acids.
Wang Yanli's team has been working on the study of the antiviral mechanism of the CRISPR-Cas system, and previous studies have revealed the important role of the CRISPR-Cas system (Nature 2014, Cell 2015, Cell Res.2016, Cell Res.2017a, Cell 2017b, Mol.Cell 2017), which is also an important development of the long-term cooperation between Wang Yanli and Zhang New Deal (Cell Res 2016, Cell 2017b).
CRISPR-Cas system is a rna-mediated acquired immune system widely present in pronuclear organisms.
, the Type III CRISPR-Cas system is the oldest and most complex of all CRISPR-Cas systems found.
A subtype in the type III CRISPR-Cas system has an effect complex called Csm, which consists of multiple Cas proteins and crRNA.
different from other CRISPR effect complexes, Csm complex seisps not only the purpose RNA complementary to crRNA, but also the binding of the purpose RNA to activate the Csm complex to produce two new enzyme activities, namely, the cutting of ssDNA in the transcription process and the activity of synthetic ring-like oligonosine (cOA).
cOA as a second messenger can activate Csm6, nonspecific degradation of RNA.
, however, the current type III-A CRISPR-Cas system Csm effect complex assembly method, identification of "self" and "non-i" DNA, as well as the activation of Csm1 DNA enzymes and adenosine cycloses and other molecular mechanisms are still unclear.
structural biology of Csm complexes in the type III-A CRISPR-Cas system.
the electromirror structure of the A. Csm-cognate target RNA-AMPPNP complex.
pattern diagram of the B. III-A CRISPR-Cas system against the invasion of external nucleic acids.
the study reported on the high-resolution crystal structure of Csm, a type III-A effect complex of streptococcus streptococcus, and the near-atomic-resolution cryoscope structure of Csm in a state of binding state to seven different elements of the purpose RNA and ATP.
studies show that the Csm complex consists of Csm1-5 five protein subkeys and a crRNA, and found that the composition of the Csm complex will change with the length of crRNA, but the composition of the five Csm proteins has been followed by the csm112n3n s14151.
the study selected 3' complementary and non-complementary purpose RNA, and found that the complementary pairing of purpose RNA and crRNA at (-2)-(-5) bits was a key factor in activating Csm1 cutting ssDNA and synthesizing cOA.
, the study found that the binding of 3' non-complementary purpose RNA led to conformational changes in the csm1 local region, thus activating the activity of Csm1's DNA enzyme and adenosine cyclate through a non-structural effect.
this study is another major breakthrough in the anti-viral mechanism of CRISPR-Cas system, further expounding the molecular mechanism of multi-protein effect complex to identify and cut exogenous nucleic acids, and laying an important theoretical foundation for the development of the TYPE III CRISPR system as an application tool.
Wang Yanli and Zhang New Deal are co-authors of this article.
Yu Lilan (PhD) (PhD) of wang Yanli Group, Wang Jiyu (Associate Researcher) and Ma Jun (Associate Researcher) of Zhang Xinying Group are the co-authors of the paper, and the study was supported by the Ministry of Science and Technology, the National Natural Science Foundation, the Chinese Academy of Sciences Strategic Pilot Science and Technology Special (Class B), the National Youth Millennium Project and the HHMI-Wellcome Fund.
Source: Institute of Biophysics.