Search

Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the activities of 5' AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR), respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G-protein-coupled receptors. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9 and 2.4 A resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of G-protein-coupled receptors, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the carboxy-terminal tail, of the receptors. The present information will facilitate the understanding of novel structure-function relationships and the development and optimization of AdipoR agonists for the treatment of obesity- related diseases, such as type 2 diabetes., Adiponectin (encoded by ADIPOQ in humans) (1-4) is an anti-diabetic adipokine. Plasma adiponectin levels are reduced in obesity and type 2 diabetes (5), while the replenishment of adiponectin reportedly ameliorated [...]

In various cellular membrane systems, vacuolar ATPases (V-ATPases) function as proton pumps, which are involved in many processes such as bone resorption and cancer metastasis, and these membrane proteins represent [...]

Thermus thermophilus [[sigma].sup.E], an extracytoplasmic function [sigma] factor from the extremely thermophilic bacterium Thermus thermophilus HB8, bound to the RNA polymerase core enzyme and showed transcriptional activity. With the combination of in vitro transcription assay and GeneChip technology, we identified three promoters recognized by [[sigma].sup.E]. The predicted consensus promoter sequence for [[sigma].sup.E] is 5'-CA(A/T)(A/C)C(A/C)-[N.sub.15]-CCGTA-3'.

Translation elongation factor P (EF-P) stimulates ribosomal peptidyltransferase activity. EF-P is conserved in bacteria and is essential for cell viability. Eukarya and Archaea have an EF-P homologue, eukaryotic initiation factor 5A (elF-5A). In the present study, we determined the crystal structure of EF-P from Thermus thermophilus HB8 at a 1.65-[Angstrom] resolution. EF-P consists of three [beta]-barrel domains (I, II, and III), whereas elF-5A has only two domains (N and C domains). Domain I of EF-P is topologically the same as the N domain of elF-5A. On the other hand, EF-P domains II and III share the same topology as that of the elF-5A C domain, indicating that domains II and III arose by duplication. Intriguingly, the N-terminal half of domain II and the C-terminal half of domain III of EF-P have sequence homologies to the N- and C-terminal halves, respectively, of the elF-5A C domain. The three domains of EF-P are arranged in an 'L' shape, with 65- and 53-[Angstrom]-long arms at an angle of 95[degrees], which is reminiscent of tRNA. Furthermore, most of the EF-P protein surface is negatively charged. Therefore, EF-P mimics the tRNA shape but uses domain topologies different from those of the known tRNA-mimicry translation factors. Domain I of EF-P has a conserved positive charge at its tip, like the elF-5A N domain.

A heteronuclear-nuclear magnetic resonance spectroscopy was used to solve the solution structure of the murine T cell intracellular antigen-1 RNA recognition motifs (TIA-1 RRM2). The similarities observed between the RNA-binding modes of the TIA-1 RRM2 and the U2AF65 RRM2 provides better understanding of the RNA recognition manner of TIA-1.

Results demonstrate that phosphotyrosyl peptides exhibit favorable binding affinity for the SH2 domian of growth factor receptor binding protein 2 as determined by molecular dynamics, free energy and surface plasmon resonance analyses. Furthermore, van der Waals interaction between the growth factor and peptides plays a major role in the specificity and binding affinity.