Upon phagocytosis, Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of L. pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of L. pneumophila and delineates the underlying molecular mechanism.
Background:The heterodimeric GTR GTPase is a key regulator in the amino acid mediated TORC1 pathway. Results: The structure of Gtr1p GTP -Gtr2p GDP reveals a large conformational change in comparison with that of Gtr1p GMPPNP -Gtr2p GMPPNP .
Conclusion:The heterodimeric GTR GTPase serves as a novel molecular switch regulating the Raptor binding affinity. Significance: The structural information leads to a better understanding of the regulatory mechanism of the GTR GTPase.
Background: Generalized granuloma annulare (GGA) is a benign skin disorder of an unknown etiology. Though some cases of GGA have been reported, few systemic reviews of the clinical and pathological features of GGA have been performed. Objective: The purpose of this study is to analyze and correlate the clinical and pathological characteristics of GGA in Korean patients. Methods: We conducted a retrospective study that included 54 biopsy specimens of Korean GGA patients, and the clinical and pathological features of GGA were reviewed and analyzed for their correlation. Results: The cutaneous lesions could be divided into the annular (24, 44%) and nonannular types (30, 56%), and the lesions were more common in males than in females (29 males and 25 females). The incidence of GGA showed a bimodal age distribution. The number of patients who presented within the first decade was 24 cases (44%), and 24 cases (44%) were over the fifth decade. Eight patients (15%) had systemic diseases. Especially, diabetes mellitus (DM) occurred only in the adult GGA patients over forty years old. The pathological findings showed dermal granulomatous lesions that consisted of either a palisading pattern (28, 52%) or an interstitial pattern (26, 48%). Conclusion: In contrast to the previously reported studies, the age of GGA onset showed a bimodal distribution, and GGA was observed more often in males. The prevalence of DM in the GGA affected individuals was higher than that found in the general Korean population. Therefore, it is recommended to perform a work-up for DM in the GGA affected patients who are over forty years old. (Ann Dermatol 21(2) 113∼119, 2009)
Wide variations in port-wine stains and their responses to various therapies pose a need for the development of an objective method to evaluate the effects of treatment. Several techniques such as laser Doppler, reflectance spectrometry, and tristimulus colorimetry have been used to evaluate the color of port-wine stains, but these techniques are limited by cost, small test size area, and other factors. Therefore, we developed a simple and cost-effective method of evaluating treatment results on port-wine stains using the L*a*b* color coordinate system in combination with a personal computer. For 22 patients with port-wine stains, the slide photographs were digitized using a slide scanner. L*a*b* color differences of the normal control and port-wine stain sites were obtained before and after treatment, and treatment effect (percent) was calculated. By calculating each color difference between the lesion and normal skin both before and after treatment, problems arising from different illuminating conditions during photography were minimized. The results were compared with the visual evaluation conducted by three experienced plastic surgeons. The treatment effects analyzed by L*a*b* color coordinate ranged from 4 to 95 percent, with a mean of 48.1 percent, whereas treatment effects evaluated by the plastic surgeons ranged from 15 to 92 percent, with a mean of 51.1 percent. The subjective clinical grades correlated well with the treatment effects obtained by the proposed color analysis system (correlation coefficient, 0.89). The maximum difference in the effect of treatment for a patient evaluated by the three clinicians was up to 60 percent, which means that visual judgment is very subjective and variable. The color analysis system proposed as a result of this study is very easy, objective, quantitative, cost-effective, and can be useful for the evaluation of treatment effects on colored skin lesions such as port-wine stains.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.