The Switch on the RAPper's Necklace…
Department of Molecular Genetics, University of Texas Southwestern, Dallas, Texas 75390, USA.Molecular Cell (Impact Factor: 14.02). 09/2006; 23(4):451-5. DOI: 10.1016/j.molcel.2006.07.026
The biosynthesis and export of LDL receptor-related proteins rely on specialized chaperones in the endoplasmic reticulum. Two recent papers in Molecular Cell by Fisher et al. (2006) and Lee et al. (2006) reveal a novel mechanism by which one of these chaperones, the receptor-associated protein RAP, accomplishes this task.
Conference Paper: Analytical inversion formula for attenuated fan-beam projections[Show abstract] [Hide abstract]
ABSTRACT: In single photon emission computed tomography (SPECT), photon attenuation within the body is a major factor contributing to the quantitative inaccuracy in measuring the in vivo distribution of radioactivity. Usually the attenuation of the body is not uniform, but for brain imaging, it can be a good approximation to assume that the attenuation is uniformly distributed. For 2D parallel-beam geometry, an exact convolution backprojection algorithm to reconstruct image from attenuated Radon transform with constant attenuation had been developed by Tretiak and Metz (1980). The algorithm can be modified for attenuated fan-beam projections. Unlike the attenuated parallel-beam projections, the filter for attenuated fan-beam projections is no longer spatially invariant, instead, it is a space-variant filter. The algorithm with this spatially variant filter will take more computation time than the algorithm with convolution, but is an exact algorithm. This algorithm has been implemented and simulated using a mathematical phantom. Compared with parallel-beam reconstructions, fan-beam reconstructions have the same image quality
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ABSTRACT: The low-density lipoprotein receptor-related protein (LRP) binds a range of proteins including receptor associated protein (RAP), activated alpha2-macroglobulin (alpha2M*), factor IXa (FIXa), and factor VIII (FVIII) light chain. The binding is mediated by the complement-type repeats, which are clustered in four distinct regions within LRP. Cluster II of 8 repeats (CR3-10) and cluster IV of 11 repeats (CR21-31) have been implicated in ligand-binding. Previous studies have aimed to identify the cluster II repeats involved in binding alpha2M* and RAP. We now evaluated the binding to RAP, alpha2M*, FIXa and FVIII light chain of triplicate repeat-fragments of not only clusters II but also of cluster IV. Employing surface plasmon resonance analysis, we found that most efficient ligand-binding was displayed by the repeats within region CR4-8 of cluster II and within region CR24-28 of cluster IV. Whereas the binding to RAP could be attributed to two consecutive repeats (CR5-6, CR26-27), combinations of three repeats showed most efficient binding to FIXa (CR6-8, CR26-28), FVIII light chain (CR5-7, CR6-8, CR24-26), and alpha2M* (CR4-6, CR24-26). The results imply that there is an internal functional duplication of complement-type repeats within LRP resulting in two clusters that bind the same ligands.
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ABSTRACT: Proteins of the low-density lipoprotein receptor family transport cholesterol-carrying particles into cells, clear protease-inhibitor complexes from the circulation, participate in biological signaling cascades, and even serve as viral receptors. These receptors utilize clusters of cysteine-rich LDL receptor type-A (LA) modules to bind many of their ligands. Recent structures show that these modules typically exhibit a characteristic binding mode to recognize their partners, relying primarily on electrostatic complementarity and avidity effects. The dominant contribution of electrostatic interactions with small interface areas in these complexes allows binding to be regulated by changes in pH via at least two distinct mechanisms. The structure of the subtilisin/kexin family protease PCSK9, a newly identified molecular partner of the LDLR also implicated in LDL-cholesterol homeostasis, also raises the possibility that the LDLR and its related family members may employ other strategies for pH-sensitive binding that have yet to be uncovered.
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