Structural studies of a bacterial condensin complex reveal ATP-dependent disruption of intersubunit interactions.

Condensins are key mediators of chromosome condensation across organisms. Like other condensins, the bacterial MukBEF condensin complex consists of an SMC family protein dimer containing two ATPase head domains, MukB, and two interacting subunits, MukE and MukF. We report complete structural views of the intersubunit interactions of this condensin along with ensuing studies that reveal a role for the ATPase activity of MukB. MukE and MukF together form an elongated dimeric frame, and MukF's C-terminal winged-helix domains (C-WHDs) bind MukB heads to constitute closed ring-like structures. Surprisingly, one of the two bound C-WHDs is forced to detach upon ATP-mediated engagement of MukB heads. This detachment reaction depends on the linker segment preceding the C-WHD, and mutations on the linker restrict cell growth. Thus ATP-dependent transient disruption of the MukB-MukF interaction, which creates openings in condensin ring structures, is likely to be a critical feature of the functional mechanism of condensins.

Impact of symptom variability on clinical outcomes in COPD: analysis of a longitudinal cohort.

Purpose: We compared clinical characteristics of COPD patients according to symptom variability and evaluated the effect of symptom variability during the first year of enrollment on clinical outcomes of COPD. Methods: We analyzed COPD patients' data from the Korean Obstructive Lung Disease (KOLD) cohort. Symptom variability was defined based on the value of standard deviation (SD) of mMRC scores obtained every 3 months during the follow-up period of the first year. Patients were divided into 2 groups: the consistent (SD of mMRC scores =0) and variable (SD of mMRC scores >0) groups. Clinical characteristics and outcomes were compared in terms of symptom variability. Results: A total of 407 patients were included in the analysis. Patient age was 67.2 years and 97.8% of the subjects were male. Initial mMRC was 1.5 and the SD of mMRC scores during the first year was 0.5. There were 137 subjects (33.7%) in the consistent group and 270 (66.3%) in the variable group. The variable group showed a lower FEV1 (P=0.019) and a higher mMRC score (P=0.001). The annual incidence of acute exacerbation of COPD (AE-COPD) tended to be higher in the variable group (P=0.078) and that of severe AE-COPD was higher in the variable group than in the consistent group (P=0.002). The variable group showed a higher proportion of annual exacerbators (P=0.001) and frequent exacerbators (P=0.017). In multivariate logistic regression analysis, the variable group was significantly associated with annual exacerbators (OR =1.963, P=0.011) and frequent exacerbators (OR =2.090, P=0.055). Conclusion: COPD patients with symptom variability may have higher exacerbation risk as well as lower lung function and more severe respiratory symptoms.