Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6.

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-CTMGI-2B16B6/MafI2MGI-2B16B6 complex from N. meningitidis B16B6. MafB2-CTMGI-2B16B6 displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CTMGI-2B16B6 forms a 1:1 complex with MafI2MGI-2B16B6 with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2MGI-2B16B6 with the substrate binding surface of MafB2-CTMGI-2B16B6 suggests that MafI2MGI-2B16B6 inhibits MafB2-CTMGI-2B16B6 by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CTMGI-2B16B6 has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CTMGI-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 MafB2MGI-2B16B6 is the enzymatic activity degrading ribonucleotides.

Experiences of physical complications and sequelae among living liver donors.

Background: This study aimed to investigate the aspects of physical complications and sequelae of living liver donors in the context of the Korean culture. A deeper understanding of these experiences will provide basic data necessary for medical management programs for living liver donors and for those expecting to become living liver donors. Methods: We used a descriptive ethnographic research method through in-depth interviews and participant observation. Data were collected from January 2016 to December 2017, till adequate quantity of data was obtained. Data were collected from 11 living liver donors using the "snow ball" method. In-depth interviews were conducted two to five times per participant, and the duration of each interview was 2 to 3 hours. Results: The results were organized into one domain, three categories, and 12 subcategories. The domain of "physical sequelae remaining after donation" was derived from "experience of internal organ disorders," "long-lasting chronic pain," "decrease in immunity and increase in disease incidence." The experiences of "experience of internal organ disorder" were described as feelings of physical constraints similar to being disabled, 100% recovery to predonation status is not possible, markedly different stamina compared to that before donation, and fatigue, with increased difficulty in performing the activities of daily life. Conclusions: Provision of appropriate medical care and continuous and systematic health care consultation before and after donation, and development of adequate support systems for donors are essential.