Guanosine nucleotide-binding proteins G-protein

Salts of the tetrafluoroaluminate (TFA) anion have been known for many years. Yet aqueous routes to pure materials have not been established despite the substantial amount of literature available on the subject. The present review will discuss the various synthetic methods that have been employed and will demonstrate a revised method for preparing pure TFA salts. These materials are important because TFA is able to stimulate various guanosine nucleotide-binding proteins (G-proteins) and inhibit P-type ATPases by serving as a nonhydrolyzing phosphate mimic. Additionally, various TFA salts serve as precursors to aluminum trifluoride, which is used as a catalyst for chlorofluorocarbon isomerizations and fluorinations. 

G-proteins or guanosine-nucleotide-binding proteins are proteins involved in a diverse range of cellular processes such as signal transduction, vesicular transport, proliferation, differentiation, cell cycle, or nuclear import. G-proteins can be divided in two main classes the heterotrimeric G-proteins (formed by three... 

The most common second messenger activated by protein/peptide hormones and catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 10.1. The process begins when the hormone binds to its receptor. These receptors are quite large and span the plasma membrane. On the cytoplasmic surface of the membrane, the receptor is associated with a G protein that serves as the transducer molecule. In other words, the G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. These proteins are referred to as G proteins because they bind with guanosine nucleotides. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone... 

G-proteins are so called because they bind a guanosine nucleotide, either GTP or GDP. Their transduction mechanism involves the production of a second messenger such as 3 5 cAMP, 3 5 cyclic GMP (cGMP) or IP3 and diacylglycerol (DAG), derived from AMP, GMP and phosphatidyl inositol-3,5bisphosphate respectively (Figure 4.15). It is the second messenger that initiates the downstream amplification process phase of transduction. 

G proteins comprise several families of diverse cellular proteins that subserve an equally diverse array of cellular functions. These proteins derive their name from the fact that they bind the guanine nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP) and possess intrinsic GTPase activity. G proteins play a central role in signal transduction as well as in a myriad of cellular processes, including membrane vesicle transport,... 

Structural studies on Ago proteins revealed that the so-called MID domain binds the 5 end of the guide strand (39,40). Because of its central localization in the Ago protein, this domain has been named MID domain. Crystal co-structures and Kj measurements of the MID domain in combination with all four nucleotides at the 5 end revealed that uridine (U) binds with the highest affinity to the MID domain, adenosine (A) with a slightly reduced affinity, and cytosine (C) and guanosine (G) with more than tenfold less affinity (41). Therefore, siRNA guide (antisense) strands should ideally contain a U or A at the 5 end. C and G should be avoided. For the passenger (sense) strand 5 end, C and G should be selected in order to minimize strand incorporation (Fig. la). Based on our own unpublished data the nucleotide specificity is not only a tool to manipulate strand selection but siRNA strands with U or A at the 5 end show also a higher absolute affinity for Ago proteins and therefore are more likely to be potent siRNAs (see Notes 2 and 3). 

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