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991.
Lammich S Kamp F Wagner J Nuscher B Zilow S Ludwig AK Willem M Haass C 《The Journal of biological chemistry》2011,286(52):45063-45072
Anti-amyloidogenic processing of the amyloid precursor protein APP by α-secretase prevents formation of the amyloid-β peptide, which accumulates in senile plaques of Alzheimer disease patients. α-Secretase belongs to the family of a disintegrin and metalloproteases (ADAMs), and ADAM10 is the primary candidate for this anti-amyloidogenic activity. We recently demonstrated that ADAM10 translation is repressed by its 5'-UTR and that in particular the first half of ADAM10 5'-UTR is responsible for translational repression. Here, we asked whether specific sequence motifs exist in the ADAM10 5'-UTR that are able to form complex secondary structures and thus potentially inhibit ADAM10 translation. Using circular dichroism spectroscopy, we demonstrate that a G-rich region between nucleotides 66 and 94 of the ADAM10 5'-UTR forms a highly stable, intramolecular, parallel G-quadruplex secondary structure under physiological conditions. Mutation of guanines in this sequence abrogates the formation of the G-quadruplex structure. Although the G-quadruplex structure efficiently inhibits translation of a luciferase reporter in in vitro translation assays and in living cells, inhibition of G-quadruplex formation fails to do so. Moreover, expression of ADAM10 was similarly repressed by the G-quadruplex. Mutation of the G-quadruplex motif results in a significant increase of ADAM10 levels and consequently APPsα secretion. Thus, we identified a critical RNA secondary structure within the 5'-UTR, which contributes to the translational repression of ADAM10. 相似文献
992.
Gutsch R Kandemir JD Pietsch D Cappello C Meyer J Simanowski K Huber R Brand K 《The Journal of biological chemistry》2011,286(26):22716-22729
993.
The human fungal pathogen, Candida albicans can grow in at least three different morphologies: yeast, pseudohyphae and hyphae. Further morphological forms exist during colony switching, for example, opaque phase cells are oblong, rather than the oval shape of yeast cells. Pseudohyphae and hyphae are both elongated and sometimes there has been little attempt to distinguish between them, as both are "filamentous forms" of the fungus. We review here the differences between them that suggest that they are distinct morphological states. We argue that studies on "filamentous forms" should always include a formal analysis to determine whether the cells are hyphae or pseudohyphae and we suggest some simple experimental criteria that can be applied to achieve this. 相似文献
994.
Chaperonins are key components of the cellular chaperone machinery. These large, cylindrical complexes contain a central cavity that binds to unfolded polypeptides and sequesters them from the cellular environment. Substrate folding then occurs in this central cavity in an ATP-dependent manner. The eukaryotic chaperonin TCP-1 ring complex (TRiC, also called CCT) is indispensable for cell survival because the folding of an essential subset of cytosolic proteins requires TRiC, and this function cannot be substituted by other chaperones. This specificity indicates that TRiC has evolved structural and mechanistic features that distinguish it from other chaperones. Although knowledge of this unique complex is in its infancy, we review recent advances that open the way to understanding the secrets of its folding chamber. 相似文献
995.
Wright SW Carlo AA Danley DE Hageman DL Karam GA Mansour MN McClure LD Pandit J Schulte GK Treadway JL Wang IK Bauer PH 《Bioorganic & medicinal chemistry letters》2003,13(12):2055-2058
3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design. 相似文献
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