Crystal Structures of the HslVU Peptidase–ATPase Complex Reveal an ATP-Dependent Proteolysis Mechanism

AbstractBackground: The bacterial heat shock locus HslU ATPase and HslV peptidase together form an ATP-dependent HslVU protease. Bacterial HslVU is a homolog of the eukaryotic 26S proteasome. Crystallographic studies of HslVU should provide an understanding of ATP-dependent protein unfolding, translocation, and proteolysis by this and other ATP-dependent proteases.Results: We present a 3.0 Å resolution crystal structure of HslVU with an HslU hexamer bound at one end of an HslV dodecamer. The structure shows that the central pores of the ATPase and peptidase are next to each other and aligned. The central pore of HslU consists of a GYVG motif, which is conserved among protease-associated ATPases. The binding of one HslU hexamer to one end of an HslV dodecamer in the 3.0 Å resolution structure opens both HslV central pores and induces asymmetric changes in HslV.Conclusions: Analysis of nucleotide binding induced conformational changes in the current and previous HslU structures suggests a protein unfolding–coupled translocation mechanism. In this mechanism, unfolded polypeptides are threaded through the aligned pores of the ATPase and peptidase and translocated into the peptidase central chamber

Use of proton pump inhibitor and risk of colorectal cancer: A meta-analysis of observational studies

Background: Previous case-control studies have reported inconsistent findings regarding the association between proton pump inhibitor (PPI) use and colorectal cancer (CRC) risk. We investigated these associations using meta-analysis. Methods: We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in April 2011. Two evaluators independently reviewed and selected articles, based on pre-determined selection criteria. Results: Out of 737 articles meeting our initial criteria, 5 case-controlstudies, which involved 120,091 participants (9,514 cases and 110,577 controls), were included in the final analyses. The overall use of PPI (used vs. never or rarely used) was not significantly associated with the risk of CRC in a fixed-effects model meta-analysis of all 5 case-control studies (odds ratio [OR], 1.08; 95%confidence interval [CI], 0.96 to 1.20; I2 = 3.5%). Also, in sensitivity meta-analysis by cumulative duration of PPI use, there was no association between PPI use of 1 year or longer and the risk of colorectal cancer in a fixed-effects meta-analysis (OR, 1.09; 95%CI, 0.98 to 1.22; I2 = 0%). Conclusion: Although hypergastrinemia could be an important factor in the pathogenesis of some colorectal cancers, our study suggests that this does not lead to significant clinical risk for most PPI users. Further prospective studies or randomized controlled trials related to PPI use and colorectal cancer risk are needed to investigate this association. © 2012 The Korean Academy of Family Medicine.Y

Bilateral teleoperation for linear force sensorless 3D robots

It is well known that for bilateral teleoperation, force feedback information is needed. In this paper, we propose a control approach for bilateral teleoperation with uncertainties in the model of the slave robot and which does not use force sensors for haptic feedback. The controller design is based on a cyclic switching algorithm. In the first phase of the cyclic algorithm, we estimate the environmental force acting on the slave robot and in the second phase a tracking controller ensures that the position of the slave robot is tracking the position of the master robot. A stability analysis of the overall closed-loop system is presented and the approach is illustrated by means of an example