#Pbp3 e coli s307 full#

Following the movement of DHE we observed that OSBP overexpression prevented retrograde movement of exogenous sterol to lipid droplets. These findings imply that OSBP like Osh4p is capable of extracting and transport PI(4)P from Golgi membranes. This decrease was found to be dependent on 25- OH binding and mutation of residues in OSBP corresponding to residues that are implied in PI(4)P binding in Osh4p, as well as deletion of the ORD. Trying to link this relocalization to a molecular function, we observed the Golgi PI(4)P level with a tagged version of the PH domain of OSBP, and we found that the levels were significantly decreased when OSBP was overexpressed. (Article Figure 2) Interestingly, OSBP was capable of tethering artificial membranes in the absence of 25-OH in vitro. Using giant unilamellar vesicles, bead-supported bilayers and small liposomes we showed by transmission electron microscopy, fluorescence microscopy and dynamic light scattering that the PH-FFAT tandem efficiently aggregated functionalized bilayers containing VAP-A or Arf1-GTP and PI(4)P, respectively.

#Pbp3 e coli s307 full#

For the full length protein, this targeting is however controlled by binding of 25- OH (Article Figure 1).

вЂњA Four-Step Cycle Driven by PI(4)P Hydrolysis Directs Sterol/PI(4)P Exchange by the ER-Golgi Tether OSBPвЂќДЄnalyzing the architecture of OSBP, we were able to show that the N-terminal region, containing the PH domain and the FFAT motif are responsible for the targeting to these perinuclear structures that we identified to be ER-Golgi contact sites by thin-section electron microscopy. However, both FKBPs appear to be also important for later stages of post-ER trafп¬Ѓcking of ABC transporters to the PM and, at least for FKBP42/TWD1, a regulatory impact on the activity of PM-resident ABCB1 has been shown. While for FKBP38-CFTR, convincing evidence shows that CFTR biogenesis mainly relies on the PPIase activity of FKBP38, this has not yet been established for FKBP42/TWD1. 2 ), where they contribute to an early step of quality control of nascent ABCs. The picture that emerges is that multido- main FKBPs, here represented by FKBP38 and FKBP42/TWD1, are key regulators of CFTR and ATA biogenesis (Fig. We have also dissected the PPIase-de- pendent and independent impact on ABC trafп¬Ѓcking and activity. We have uncovered surprising functional similarities, but also a few differences, between regulatory FKBP42/ TWD1-ABCB and FKBP38-CFTR modules in plants and mammals. In this perspective article, we have summarized and critically evaluated the current knowledge on ABC transporter regulation by multidomain FKBPs.