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Translocator Proteins (translocator + protein)
Selected AbstractsThe development of PET radioligands for imaging the translocator protein (18,kDa): What have we learned?JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2010Christopher Luus Abstract The translocator protein (TSPO; 18,kDa), formerly known as the peripheral benzodiazepine receptor (PBR), is minimally expressed in the healthy brain. On the other hand, increased levels of TSPO have been noted in brain disorders for which an immune response is elicited. This increase in TSPO expression has been reported to coincide with the process of microglial activation making the measurement of TSPO density a useful indicator of active brain disease. To this end several new classes of TSPO positron emission tomography radioligands have been developed and evaluated. However, the incomplete pharmacological characterization of the TSPO and its ligands as well as differences in pathophysiology, pharmacology and molecular nature across species and tissue types means that caution must be exercised when comparing data obtained with various TSPO radioligands. A re-evaluation of our interpretation of imaging data, which better correlates with our current understanding of TSPO pharmacology in disease, requires consideration. Copyright © 2010 John Wiley & Sons, Ltd. [source] Near-atomic resolution analysis of BipD, a component of the type III secretion system of Burkholderia pseudomalleiACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010M. Pal Burkholderia pseudomallei, the causative agent of melioidosis, possesses a type III protein secretion apparatus that is similar to those found in Salmonella and Shigella. A major function of these secretion systems is to inject virulence-associated proteins into target cells of the host organism. The bipD gene of B. pseudomallei encodes a secreted virulence factor that is similar in sequence and is most likely to be functionally analogous to IpaD from Shigella and SipD from Salmonella. Proteins in this family are thought to act as extracellular chaperones at the tip of the secretion needle to help the hydrophobic translocator proteins enter the target cell membrane, where they form a pore and may also link the translocon pore with the secretion needle. BipD has been crystallized in a monoclinic crystal form that diffracted X-rays to 1.5,Å resolution and the structure was refined to an R factor of 16.1% and an Rfree of 19.8% at this resolution. The putative dimer interface that was observed in previous crystal structures was retained and a larger surface area was buried in the new crystal form. [source] Crystallization and preliminary X-ray diffraction analysis of BipD, a virulence factor from Burkholderia pseudomalleiACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2006M. J. Knight Burkholderia pseudomallei, the causative agent of melioidosis, possesses a protein-secretion apparatus that is similar to those found in Salmonella and Shigella. A major function of these secretion systems is to secrete virulence-associated proteins into target cells of the host organism. The BipD gene of B. pseudomallei encodes a secreted virulence factor that is similar in sequence and most likely functionally analogous to IpaD from Shigella and SipD from Salmonella. Thus, the BipD protein is likely to be a component of a type III protein-secretion system (TTSS) in B. pseudomallei. Proteins in the same class as BipD, such as IpaD and SipD, are thought to act as extracellular chaperones to help the hydrophobic translocator proteins enter the target cell membrane, where they form a pore and might even link the translocon pore with the secretion needle. There is evidence that the translocator proteins also bind an integrin which stimulates actin-mediated insertion of the bacterium into the host-cell membrane. Native BipD has been crystallized in a monoclinic crystal form that diffracts X-rays to 2.5,Å resolution. BipD protein which incorporates selenomethionine (SeMet-BipD) has also been expressed and forms crystals which diffract to a higher resolution of 2.1,Å. [source] | ||||||||||