Structural insights into assembly, operation and inhibition of a type I restriction–modification system
| Autor: | Han Feng, Pu Gao, Yina Gao, Xiao-Xue Yan, Duanfang Cao, Songqing Liu, Xiu Luo, Xinzheng Zhang, Jingpeng Zhu |
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| Rok vydání: | 2020 |
| Předmět: |
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Molecular Microbiology (medical) Protein Conformation Immunology Repressor Computational biology medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Genome Viral Proteins 03 medical and health sciences Endonuclease chemistry.chemical_compound Protein structure Bacterial Proteins Escherichia coli Genetics medicine Translocase DNA Restriction-Modification Enzymes 030304 developmental biology 0303 health sciences Mutation biology 030306 microbiology Chemistry Escherichia coli Proteins Cryoelectron Microscopy Deoxyribonucleases Type I Site-Specific DNA Cell Biology DNA-Binding Proteins Repressor Proteins biology.protein Restriction modification system |
| Zdroj: | Nature Microbiology. 5:1107-1118 |
| ISSN: | 2058-5276 |
| DOI: | 10.1038/s41564-020-0731-z |
| Popis: | Type I restriction–modification (R–M) systems are widespread in prokaryotic genomes and provide robust protection against foreign DNA. They are multisubunit enzymes with methyltransferase, endonuclease and translocase activities. Despite extensive studies over the past five decades, little is known about the molecular mechanisms of these sophisticated machines. Here, we report the cryo-electron microscopy structures of the representative EcoR124I R–M system in different assemblies (R2M2S1, R1M2S1 and M2S1) bound to target DNA and the phage and mobile genetic element-encoded anti-restriction proteins Ocr and ArdA. EcoR124I can precisely regulate different enzymatic activities by adopting distinct conformations. The marked conformational transitions of EcoR124I are dependent on the intrinsic flexibility at both the individual-subunit and assembled-complex levels. Moreover, Ocr and ArdA use a DNA-mimicry strategy to inhibit multiple activities, but do not block the conformational transitions of the complexes. These structural findings, complemented by mutational studies of key intermolecular contacts, provide insights into assembly, operation and inhibition mechanisms of type I R–M systems. This study provides new insights into the structure, assembly and dynamics of type I restriction–modification systems, and their inhibition by phage proteins. |
| Databáze: | OpenAIRE |
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