Mechanism of RecF-RecO-RecR cooperation in bacterial homologous recombination.

In bacteria, one type of homologous-recombination-based DNA-repair pathway involves RecFOR proteins that bind at the junction between single-stranded (ss) and double-stranded (ds) DNA. They facilitate the replacement of SSB protein, which initially covers ssDNA, with RecA, which mediates the search for homologous sequences. However, the molecular mechanism of RecFOR cooperation remains largely unknown. We used Thermus thermophilus proteins to study this system. Here, we present a cryo-electron microscopy structure of the RecF-dsDNA complex, and another reconstruction that shows how RecF interacts with two different regions of the tetrameric RecR ring. Lower-resolution reconstructions of the RecR-RecO subcomplex and the RecFOR-DNA assembly explain how RecO is positioned to interact with ssDNA and SSB, which is proposed to lock the complex on a ssDNA-dsDNA junction. Our results integrate the biochemical data available for the RecFOR system and provide a framework for its complete understanding.

Dodecameric structure of a small heat shock protein from Mycobacterium marinum M.

Small heat shock proteins (sHSPs) are ATP-independent molecular chaperones present ubiquitously in all kingdoms of life. Their low molecular weight subunits associate to form higher order structures. Under conditions of stress, sHSPs prevent aggregation of substrate proteins by undergoing rapid changes in their conformation or stoichiometry. Polydispersity and dynamic nature of these proteins have made structural investigations through crystallography a daunting task. In pathogens like Mycobacteria, sHSPs are immuno-dominant antigens, enabling survival of the pathogen within the host and contributing to disease persistence. We characterized sHSPs from Mycobacterium marinum M and determined the crystal structure of one of these. The protein crystallized in three different conditions as dodecamers, with dimers arranged in a tetrahedral fashion to form a closed cage-like architecture. Interestingly, we found a pentapeptide bound to the dodecamers revealing one of the modes of sHSP-substrate interaction. Further, we have observed that ATP inhibits the chaperoning activity of the protein.

Onychomycosis: an Asian perspective.

Extrapolated data from epidemiologic studies of onychomycosis unique to Asia have produced intriguing revelations and opened new lines of inquiry; however, the usefulness of this research is compromised by lack of uniformity in data collection. It is proposed that a common protocol be constructed to facilitate the study ofonychomycosis, in Asia, as elsewhere, the most common disease of the nails.

Onychomycosis: a 3-year clinicomycologic hospital-based study.

BACKGROUND: Despite onychomycosis being an established entity, only a few studies are available from the Indian subcontinent. The authors investigated the comprehensive pattern of the condition. AIM: To investigate the epidemiologic, clinical, and mycologic factors associated with onychomycosis in 50 patients using a prospective study design. METHODS: Fifty patients with potassium hydroxide-positive tests were evaluated according to a predetermined protocal recording details of epidemiologic, clinical, and mycologic characteristics. The collected data were analyzed to determine the correlation of various parameters. RESULTS: Distal and lateral subungual onychomycosis, total dystrophic onychomycosis, and superficial white onychomycosis variants of onychomycosis were identified, mostly in men 21-30 years of age (mean age, 34.5 years). Epidemiologic characteristics were instrumental to either initiate, perpetuate, or disseminate the disease process. Trichophyton rubrum and Trichophyton mentagrophytes were the main causative dermatophytes; yeasts and molds were less common. CONCLUSIONS: Recognition of onychomycosis is less difficult providing the clinician is aware of the entity. Should the etiologic diagnosis be made, its eradication is desirable to surmount its implication in the society at large.