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991.
Large conductance, Ca2+-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological
processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability
of BK channels to be synergistically activated by membrane voltage, intracellular Ca2+ and other ligands. Similar to voltage-gated K+ channels, BK channels possess a pore-gate domain (S5–S6 transmembrane segments) and a voltage-sensor domain (S1–S4). In addition,
BK channels contain a large cytoplasmic C-terminal domain that serves as the primary ligand sensor. The voltage sensor and
the ligand sensor allosterically control K+ flux through the pore-gate domain in response to various stimuli, thereby linking cellular metabolism and membrane excitability.
This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca2+ - and Mg2+ -dependent activation of the channel.
Received 25 September 2008; received after revision 23 October 2008; accepted 24 October 2008 相似文献
992.
Dynamic protein methylation in chromatin biology 总被引:1,自引:1,他引:0
993.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
994.
Ronda Bransteitter Courtney Prochnow Xiaojiang S. Chen 《Cellular and molecular life sciences : CMLS》2009,66(19):3137-3147
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases has emerged as an intensively
studied field as a result of their important biological functions. These enzymes are involved in lipid metabolism, antibody
diversification, and the inhibition of retrotransposons, retroviruses, and some DNA viruses. The APOBEC proteins function
in these roles by deaminating single-stranded (ss) DNA or RNA. There are two high-resolution crystal structures available
for the APOBEC family, Apo2 and the C-terminal catalytic domain (CD2) of Apo3G or Apo3G-CD2 [Holden et al. (Nature 456:121–124,
2008); Prochnow et al. (Nature 445:447–451, 2007)]. Additionally, the structure of Apo3G-CD2 has also been determined using
NMR [Chen et al. (Nature 452:116–119, 2008); Furukawa et al. (EMBO J 28:440–451, 2009); Harjes et al. (J Mol Biol, 2009)].
A detailed structural analysis of the APOBEC proteins and a comparison to other zinc-coordinating deaminases can facilitate
our understanding of how APOBEC proteins bind nucleic acids, recognize substrates, and form oligomers. Here, we review the
recent development of structural and functional studies that apply to Apo3G as well as the APOBEC deaminase family. 相似文献
995.
A. Shukla P. Chaurasia S. R. Bhaumik 《Cellular and molecular life sciences : CMLS》2009,66(8):1419-1433
Methylation of lysine residues of histones is associated with functionally distinct regions of chromatin, and, therefore,
is an important epigenetic mark. Over the past few years, several enzymes that catalyze this covalent modification on different
lysine residues of histones have been discovered. Intriguingly, histone lysine methylation has also been shown to be cross-regulated
by histone ubiquitination or the enzymes that catalyze this modification. These covalent modifications and their cross-talks
play important roles in regulation of gene expression, heterochromatin formation, genome stability, and cancer. Thus, there
has been a very rapid progress within past several years towards elucidating the molecular basis of histone lysine methylation
and ubiquitination, and their aberrations in human diseases. Here, we discuss these covalent modifications with their cross-regulation
and roles in controlling gene expression and stability.
Received 24 September 2008; received after revision 21 November 2008; accepted 28 November 2008 相似文献
996.
V. Le Fourn K. Gaplovska-Kysela B. Guhl R. Santimaria C. Zuber J. Roth 《Cellular and molecular life sciences : CMLS》2009,66(8):1434-1445
Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated
degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins
to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout
the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved
cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified
autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting
autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation
involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies
demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol
and is degraded by basal autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009
V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work. 相似文献
997.
The elucidation of assembly pathways of multi-subunit membrane proteins is of growing interest in structural biology. In this
study, we provide an analysis of the assembly of the asymmetrically oriented PsaC subunit on the pseudo C2-symmetric Photosystem I core. Based on a comparison of the differences in the NMR solution structure of unbound PsaC with
that of the X-ray crystal structure of bound PsaC, and on a detailed analysis of the PsaC binding site surrounding the FX iron-sulfur cluster, two models can be envisioned for what are likely the last steps in the assembly of Photosystem I. Here,
we dissect both models and attempt to address heretofore unrecognized issues by proposing a mechanism that includes a thermodynamic
perspective. Experimental strategies to verify the models are proposed. In closing, the evolutionary aspects of the assembly
process will be considered, with special reference to the structural arrangement of the PsaC binding surface.
Received 22 October 2008; received after revision 17 November 2008; accepted 05 December 2008 相似文献
998.
S. Kjellev 《Cellular and molecular life sciences : CMLS》2009,66(8):1350-1369
The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing
cells – especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and
may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities
including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal
models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal
protection and repair.
Received 10 October 2008; received after revision 07 November 2008; accepted 10 November 2008 相似文献
999.
利用TH-UWB系统信号的特点,采用串行干扰消除检测方法,提出一种低复杂度的多用户检测器.该检测器采用多级检测结构,依据用户脉冲被干扰的情况来确定检测顺序,受到干扰最小的用户最先进行检测判决.前一级的检测结果反馈回来重建该用户的信号,然后从接收的信号中消除.该检测器使每级检测的处理增益最大化,从而取得较好的检测性能.理论分析和仿真结果表明,该检测器取得了远优于单用户匹配滤波检测的性能. 相似文献
1000.
讨论了不确定线性奇异系统的有限时间容错控制问题.针对一类含有时变、范数有界参数不确定奇异系统,运用线性矩阵不等式方法(LMI),设计了鲁棒容错状态反馈控制律,使得当奇异系统执行器发生故障时,故障闭环系统仍然是正则、无脉冲,且保持有限时间状态稳定,给出了有限时间容错控制器存在的充分条件和设计方法,该方法通过解线性矩阵不等式即可得到容错控制器的设计结果.数值算例验证了该容错控制设计方法的有效性. 相似文献