8x5d
The cryo-EM structure of the Mycobacterium tuberculosis CRISPR-Csm complex
Structural highlights
FunctionCSM3_MYCTU 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 spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activities (Probable). This CRISPR-Cas system protects bacteria against transformation with plasmids containing DNA homologous to its spacer regions (PubMed:29979631).[1] [2] This subunit has the target ssRNA endonuclease activity; it cleaves multiple sites in the target RNA at 6 nucleotide intervals.[UniProtKB:A0A0A7HIF0] Publication Abstract from PubMedTuberculosis (TB), a leading cause of mortality globally, is a chronic infectious disease caused by Mycobacterium tuberculosis that primarily infiltrates the lung. The mature crRNAs in M. tuberculosis transcribed from the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) locus exhibit an atypical structure featured with 5' and 3' repeat tags at both ends of the intact crRNA, in contrast to typical Type-III-A crRNAs that possess 5' repeat tags and partial crRNA sequences. However, this structural peculiarity particularly concerning the specific binding characteristics of the 3' repeat end within the mature crRNA within the Csm complex, has not been comprehensively elucidated. Here, our Mycobacteria CRISPR-Csm complexes structure represents the largest Csm complex reported to date. It incorporates an atypical Type-III-A CRISPR RNA (crRNA) (46 nt) with 5' 8-nt and 3' 4-nt repeat sequences in the stoichiometry of Mycobacteria Csm1(1)2(5)3(6)4(1)5(1.) The PAM-independent single-stranded RNAs (ssRNAs) are the most suitable substrate for the Csm complex. The 3'-repeat end trimming of mature crRNA was not necessary for its cleavage activity in Type-III-A Csm complex. Our work broadens our understanding of the Type-III-A Csm complex and identifies another mature crRNA processing mechanism in the Type-III-A CRISPR-Cas system based on structural biology. Type-III-A structure of mycobacteria CRISPR-Csm complexes involving atypical crRNAs.,Zhang H, Shi M, Ma X, Liu M, Wang N, Lu Q, Li Z, Zhao Y, Zhao H, Chen H, Zhang H, Jiang T, Ouyang S, Huo Y, Bi L Int J Biol Macromol. 2024 Mar;260(Pt 2):129331. doi: , 10.1016/j.ijbiomac.2024.129331. Epub 2024 Jan 11. PMID:38218299[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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