Download MendeleyStructural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6.
Park, S.H., Jeong, S.J., Ha, S.C.(2023) Sci Rep 13: 3365-3365
- PubMed: 36849501
- DOI: https://doi.org/10.1038/s41598-023-30528-9
- Primary Citation of Related Structures:
8HHJ - PubMed Abstract:
The Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the MGIs, the MafB and MafI encode toxin and immunity proteins, respectively. Although the C-terminal region of MafB (MafB-CT) is specific for toxic activity, the underlying enzymatic activity that renders MafB-CT toxic is unknown in many MafB proteins due to lack of homology with domain of known function. Here we present the crystal structure of the MafB2-CT MGI-2B16B6 /MafI2 MGI-2B16B6 complex from N. meningitidis B16B6. MafB2-CT MGI-2B16B6 displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CT MGI-2B16B6 forms a 1:1 complex with MafI2 MGI-2B16B6 with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2 MGI-2B16B6 with the substrate binding surface of MafB2-CT MGI-2B16B6 suggests that MafI2 MGI-2B16B6 inhibits MafB2-CT MGI-2B16B6 by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CT MGI-2B16B6 has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CT MGI-2B16B6 , suggesting that these residues are critical for its ribonuclease activity. These data provide structural and biochemical evidence that the origin of the toxic activity of MafB2 MGI-2B16B6 is the enzymatic activity degrading ribonucleotides.
Organizational Affiliation:
Beamline Department, Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, Republic of Korea.
