5wtk
From Proteopedia
Crystal structure of RNP complex
Structural highlights
FunctionCS13A_LEPSD CRISPR (clustered regularly interspaced short palindromic repeat), is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements (spacers) and target invading nucleic acids. Unlike many single-component effectors, this CRISPR-Cas system targets RNA (PubMed:27256883, PubMed:28086085). CRISPR clusters are transcribed from pre-CRISPR RNA (crRNA) and processed into crRNA (optimally 28 nucleotides in this system) by this protein (PubMed:27256883, PubMed:27669025, PubMed:28475872, PubMed:28086085). This protein processes pre-crRNA at a 'non-typical' site 1 nucleotide upstream of the pre-crRNA stem-loop; it cleaves pre-crRNA from L.buccalis and L.wadei in a similar fashion, whereas the enzymes from the latter 2 bacteria cleave their own pre-crRNA 3 nt further upstream (PubMed:28475872). When the appropriate target sequences are cloned into the CRISPR array, confers immunity to ssRNA(+) enterobacteria phage MS2 (PubMed:27256883). Cleaves linear target ssRNA in a crRNA-dependent fashion, preferentially before U residues; has no activity on partially dsRNA, ssDNA or dsDNA (PubMed:27256883). RNA secondary structure surrounding the target influence the cleavage site and efficiency; unlike other CRISPR-Cas effectors Cas13a cleaves outside of the crRNA binding site (PubMed:27256883). In the presence of a viable RNA target other RNAs are also degraded (called collateral RNA degradation), suggesting this type of CRISPR-Cas might also prevent viral spread by inducing programmed cell death or dormancy (PubMed:27256883). This system has a 3' protospacer flanking site (PFS), it does not cleave when the 3' PFS is G (PFS is equivalent to PAM, the protospacer adjacent motif) (PubMed:27256883). Mutations of its active site residues results in an RNA-programmed RNA-binding protein (PubMed:27256883).[1] [2] [3] [4] Publication Abstract from PubMedC2c2, the effector of type VI CRISPR-Cas systems, has two RNase activities-one for cutting its RNA target and the other for processing the CRISPR RNA (crRNA). Here, we report the structures of Leptotrichia shahii C2c2 in its crRNA-free and crRNA-bound states. While C2c2 has a bilobed structure reminiscent of all other Class 2 effectors, it also exhibits different structural characteristics. It contains the REC lobe with a Helical-1 domain and the NUC lobe with two HEPN domains. The two RNase catalytic pockets responsible for cleaving pre-crRNA and target RNA are independently located on Helical-1 and HEPN domains, respectively. crRNA binding induces significant conformational changes that are likely to stabilize crRNA binding and facilitate target RNA recognition. These structures provide important insights into the molecular mechanism of dual RNase activities of C2c2 and establish a framework for its future engineering as a RNA editing tool. Two Distant Catalytic Sites Are Responsible for C2c2 RNase Activities.,Liu L, Li X, Wang J, Wang M, Chen P, Yin M, Li J, Sheng G, Wang Y Cell. 2017 Jan 12;168(1-2):121-134.e12. doi: 10.1016/j.cell.2016.12.031. Epub, 2017 Jan 12. PMID:28086085[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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