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Nonglutamate pore residues in ion selection and conduction in voltage-gated Ca(2+) channels
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High-affinity, intrapore binding of Ca(2+) over competing ions is the essential feature in the ion selectivity mechanism of voltage-gated Ca(2+) channels. At the same time, several million Ca(2+) ions can travel each second through the pore of a single open Ca(2+) channel. How such high Ca(2+) flux is achieved in the face of tight Ca(2+) binding is a current area of inquiry, particularly from a structural point of view. The ion selectivity locus comprises four glutamate residues within the channel's pore. These glutamates make unequal contributions to Ca(2+) binding, underscoring a role for neighboring residues in pore function. By comparing two Ca(2+) channels (the L-type alpha(1C), and the non-L-type alpha(1A)) that differ in their pore properties but only differ at a single amino acid position near the selectivity locus, we have identified the amino-terminal neighbor of the glutamate residue in motif III as a determinant of pore function. This position is more important in the function of alpha(1C) channels than in alpha(1A) channels. For a systematic series of mutations at this pore position in alpha(1C), both unitary Ba(2+) conductance and Cd(2+) block of Ba(2+) current varied with residue volume. Pore mutations designed to make alpha(1C) more like alpha(1A) and vice versa revealed that relative selectivity for Ba(2+) over K(+) depended almost solely on pore sequence and not channel type. Analysis of thermodynamic mutant cycles indicates that the motif III neighbor normally interacts in a cooperative fashion with the locus, molding the functional behavior of the pore. 相似文献
84.
V. Y. Brodsky L. A. Malchenko D. S. Lazarev N. N. Butorina T. K. Dubovaya N. D. Zvezdina 《Biochemistry. Biokhimii?a》2018,83(3):294-298
The kinetics of protein synthesis was investigated in primary cultures of hepatocytes from old rats in serum–free medium. The rats were fed mixed fodder supplemented with glutamic acid and then transferred to a regular mixed fodder. The amplitude of protein synthesis rhythm in hepatocytes isolated from these rats increased on average 2–fold in comparison with the rats not receiving glutamic acid supplement. Based on this indicator reflecting the degree of cell–cell interactions, the cells from old rats were not different from those of young rats. The effect was preserved for 3–4 days. These results are discussed in connection with our previous data on preservation of the effect of single administration of gangliosides, noradrenaline, serotonin, and other synchronizers on various cell populations. In contrast to the other investigated factors, glutamic acid is capable of penetrating the blood–brain barrier, which makes its effect possible not only in the case of hepatocytes and other non–brain cells, but also in neurons. 相似文献
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S. S. Lazarev 《Paleontological Journal》2011,45(1):23-34
Two new tribes Chaoiellini and Rugatiini with smoothed ribs on the disk and late appearance of high corpus cavity in the phylogeny
and ontogeny are distinguished within the new subfamily Chaoiellinae. New genera Altaiproductus and Alpavlia are considered to be phyletic ancestors of Chaoiella. The latter genus is revised and redescribed. 相似文献
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B A Grishkovski? T B Khromova V S Grechishko Iu A Lazarev 《Molekuliarnaia biologiia》1991,25(1):77-82
By the IR-spectroscopy method successive stages of hydrate envelope formation of the collagen-like triple-helical structure of the monodisperse synthetic polytripeptide Z-(Gly-Pro-Pro)8-OMe were studied. The multistep-type process is followed by isomorphic transitions of the triple-helical structure and by the increasing of hydrogen bond strength. 相似文献
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