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Protein Coupling (protein + coupling)
Selected AbstractsAmino acids involved in conformational dynamics and G protein coupling of an odorant receptor: targeting gain-of-function mutationJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Aya Kato Abstract Thousands of different odorants are recognized and discriminated by odorant receptors (ORs) in the guanine nucleotide-binding protein (G protein)-coupled seven-transmembrane receptor family. Odorant-bound ORs stimulate Gs-type G proteins, G,olf, which in turn activates cAMP-mediated signaling pathway in olfactory sensory neurons. To better understand the molecular basis for OR activation and G protein coupling, we analyzed the effects of a series of site-directed mutations of mouse ORs, on function. Mutations of conserved amino acid residues in an intracellular loop or the C-terminus resulted in loss of activity without impairing ligand-binding activity, indicating that these residues are involved in G,s/olf coupling. Moreover, mutation of the serine in KAFSTC, the OR-specific sequence motif, resulted in a dramatic increase in odorant responsiveness, suggesting that the motif is involved in a conformational change of the receptor that regulates G protein coupling efficiency. Our results provide insights into how ORs switch from an inactive to an active state, as well as where and how activated ORs interact with G proteins. [source] Regulation of A2A adenosine receptor expression and functioning following permanent focal ischemia in rat brainJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Maria L. Trincavelli Abstract Ischemia, through modulation of adenosine receptors (ARs), may influence adenosine-mediated-cellular responses. In the present study, we investigated the modulation of rat A2A receptor expression and functioning, in rat cerebral cortex and striatum, following in vivo focal ischemia (24 h). In cortex, middle cerebral artery occlusion did not induce any alterations in A2A receptor binding and functioning. On the contrary, in striatum, a significant decrease in A2A ligand affinity, associated with an increase in receptor density, were detected. In striatum, ischemia also induced a significant reduction both in G protein pool and in A2A receptor-G protein coupling. On the contrary, A2A receptor functional responsiveness, measured as stimulation of adenylyl cyclise, was not affected by ischemia, suggesting receptor up-regulation may represent a compensatory mechanism to maintain receptor functioning during cerebral damage. Immunohistochemical study showed that following 24 h middle cerebral artery occlusion, A2A ARs were definitely expressed both on neurons and activated microglia in ischemic striatum and cortex, but were not detected on astrocytes. In the non-ischemic hemisphere and in sham-operated rats A2A ARs were barely detected. Modifications of ARs may play a significant role in determining adenosine effects during ischemia and therefore should be taken into account when evaluating time-dependent protective effects of specific A2A active compounds. [source] A di(bisphosphonic acid) for protein coupling and targeting to boneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2004Geeti Bansal Abstract Proteins intended for treatment of bone diseases should ideally exhibit a high bone affinity, so that they are preferentially deposited to bones after systemic administration. This can be achieved by combining molecules having a high affinity to bone with the proteins. Bisphosphonates (BPs) are chemical analogs of pyrophosphate that possess exceptional bone mineral affinity. To this end, we synthesized a novel BP, 3,5-di(ethylamino-2,2-bisphosphono)benzoic acid (6), which contains two BP moieties on a single molecule, unlike conventional BPs that contain one BP moiety per molecule. 6 was then conjugated to two model proteins, bovine serum albumin and nonspecific bovine immunoglobulin G by the carbodiimide chemistry. By varying the reagent concentrations, the conjugation efficiency (i.e., number of 6 per protein) was readily controlled under the experimental conditions. The protein- 6 conjugates exhibited an in vitro mineral affinity that was proportional to the number of conjugated 6. The 6 -conjugates of both bovine serum albumin and immunoglobulin G were found to be bone seeking in rats, based on the increased concentration of 6 -conjugated proteins in bone tissue after intravenous administration. We conclude that the novel BP synthesized (6) can serve as a carrier for bone delivery while reducing the extent of protein modification necessary for bone targeting. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2788,2799, 2004 [source] Whole protein coupling to virus-like particlesBIOTECHNOLOGY & BIOENGINEERING, Issue 5 2007Article first published online: 18 OCT 200 No abstract is available for this article. [source] | ||||||||||