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911.
The continuing disappearance of “pure” Ca2+ buffers 总被引:1,自引:1,他引:0
B. Schwaller 《Cellular and molecular life sciences : CMLS》2009,66(2):275-300
Advances in the understanding of a class of Ca2+-binding proteins usually referred to as “Ca2+ buffers” are reported. Proteins historically embraced within this group include parvalbumins (α and β), calbindin-D9k, calbindin-D28k
and calretinin. Within the last few years a wealth of data has accumulated that allow a better understanding of the functions
of particular family members of the >240 identified EF-hand Ca2+-binding proteins encoded by the human genome. Studies often involving transgenic animal models have revealed that they exert
their specific functions within an intricate network consisting of many proteins and cellular mechanisms involved in Ca2+ signaling and Ca2+ homeostasis, and are thus an essential part of the Ca2+ homeostasome. Recent results indicate that calbindin-D28k, possibly also calretinin and oncomodulin, the mammalian β parvalbumin,
might have additional Ca2+ sensor functions, leaving parvalbumin and calbindin-D9k as the only “pure” Ca2+ buffers.
Received 10 September 2008; received after revision 15 October 2008; accepted 4 November 2008 相似文献
912.
913.
L. Yin C. M. Chung R. Huo H. Liu C. Zhou W. Xu H. Zhu J. Zhang Q. Shi H. Y. C. Wong J. Chen Y. Lu Y. Bi C. Zhao Y. Du M. Ma Y. Cai W. Y. Chen K. L. Fok L. L. Tsang K. Li Y. Ni Y. W. Chung Z. Zhou J. Sha H. C. Chan 《Cellular and molecular life sciences : CMLS》2009,66(5):900-908
The acrosome reaction has long been thought to be induced by the zona pellucida. Here we report the identification and function
of a novel human sperm glycosylphosphatidylinositol (GPI)-anchored membrane protein, NYD-SP8. The release of the protein during
sperm-egg interaction and its binding to the cumulus, the first layer of egg investment, elicits cross-talk between the gametes
and produces calcium dependant release of progesterone, which lead to the acrosome reaction. An in vivo mouse model of NYD-SP8 immunization is also established showing a reduced fertility rate. Thus, contrary to accepted dogma,
our study demonstrates for the first time that, prior to reaching the zona pellucida, sperm may release a surface protein
that acts on the cumulus cells leading to the acrosome reaction, which may be important for determining the outcome of fertilization.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 11 August 2008; received after revision 18 December 2008; accepted 22 December 2008 相似文献
914.
H.-T. Zhao S. Endo S. Ishikura R. Chung P. J. Hogg A. Hara O. El-Kabbani 《Cellular and molecular life sciences : CMLS》2009,66(9):1570-1579
l-Xylulose reductase (XR) is involved in water re-absorption and cellular osmoregulation. The crystal structure of human XR
complemented with site-directed mutagenesis (Cys138Ala) indicated that the disulfide bond in the active site between Cys138
and Cys150 is unstable and may affect the reactivity of the enzyme. The effects of reducing agents on the activities of the
wild-type and mutant enzymes indicated the reversibility of disulfide-bond formation, which resulted in three-fold decrease
in catalytic efficiency. Furthermore, the addition of cysteine (>2 mM) inactivated human XR and was accompanied by a 10-fold
decrease in catalytic efficiency. TOF-MS analysis of the inactivated enzyme showed the S-cysteinylation of Cys138 in the wild-type
and Cys150 in the mutant enzymes. Thus, the action of human XR may be regulated by cellular redox conditions through reversible
disulfide-bond formation and by S-cysteinylation.
Received 25 January 2009; received after revision 12 February 2009; accepted 16 February 2009
H.-T. Zhao, S. Endo: These two authors contribute equally to this work. 相似文献
915.
生物信息学分析显示,拟南芥基因At5g62390编码一种钙调素结合蛋白,在其钙调素结合结构域有一个BAG(Bcl-2-associated athnogene)结构域存在,与钙调素结构域部分重叠.为了从实验上进一步研究该蛋白的钙调素结合特征及BAG结构域在钙调素结合中可能的调节作用,通过聚合酶链式反应(PCR)扩增不同结构域编码区的cDNA序列,构建到原核表达载体pET32-a中.测序分析表明:目的序列已正确克隆到表达载体上,为进一步表达目的蛋白及其不同结构域用于生化功能鉴定打下了基础. 相似文献
916.
The polypyrimidine tract binding protein (PTB) is a 58-kDa RNA binding protein involved in multiple aspects of mRNA metabolism
including splicing regulation, polyadenylation, 3′end formation, internal ribosomal entry site-mediated translation, RNA localization
and stability. PTB contains four RNA recognition motifs (RRMs) separated by three linkers. In this review we summarize structural
information on PTB in solution that has been gathered during the past 7 years using NMR spectroscopy and small-angle X-ray
scattering. The structures of all RRMs of PTB in their free state and in complex with short pyrimidine tracts, as well as
a structural model of PTB RRM2 in complex with a peptide, revealed unusual structural features that provided new insights
into the mechanisms of action of PTB in the different processes of RNA metabolism and in particular splicing regulation.
Received 16 August 2007; received after revision 18 September 2007; accepted 2 October 2007 相似文献
917.
Pozza A Perez-Victoria JM Sardo A Ahmed-Belkacem A Di Pietro A 《Cellular and molecular life sciences : CMLS》2006,63(16):1912-1922
Human ABCG2 was efficiently overexpressed in insect cell membranes, solubilized with 3-[(3-cholamidopropyl)dimethyl ammonio]-1-propanesulfonate,
and purified through N-terminal hexahistidine tag. Its functionality was assessed by high vanadate-sensitive ATPase activity, and nucleotide-binding
capacity. Interestingly, the R482T point mutation increased both maximal hydrolysis rate and affinity for MgATP, and lowered
sensitivity to vanadate inhibition. Direct nucleotide binding, as monitored by quenching of intrinsic fluorescence, indicated
a mutation-related preference for ATP over ADP. The R482T mutation only produced a limited change, if any, on the binding
of drug substrates, indicating that methotrexate, on the one hand, and rhodamine 123 or doxorubicin, on the other hand, bound
similarly to wild-type and mutant transporters whether or not they were subject to cellular transport. In addition, the characteristic
inhibitors GF120918 and 6-prenylchrysin, which alter mitoxantrone efflux much better for wild-type than mutant ABCG2, bound
similarly to purified ABCG2, while the highly-potent Ko143 bound in the nanomolar range also effective in inhibition of drug
transport. All results indicate that the role of the arginine-482 mutation on substrate drug transport and inhibitor efficiency
is not mediated by changes in drug binding.
Received 10 April 2006; received after revision 22 May 2006; accepted 12 June 2006
A. Pozza and J. M. Perez-Victoria contributed equally to this work 相似文献
918.
919.
Cowan-Jacob SW 《Cellular and molecular life sciences : CMLS》2006,63(22):2608-2625
Our current understanding of the structure, mechanism of action and modes of regulation of the protein tyrosine kinase family
owes a great deal to structural biology. Structures are now available for more than 20 different tyrosine kinase domains,
many of these in multiple conformational states. They form the basis for the design of experiments to further investigate
the role of different structural elements in the normal function and regulation of the protein and in the pathogenesis of
many human diseases. Once thought to be too similar to be specifically inhibited by a small molecule, structural differences
between kinases allow the design of compounds which inhibit only an acceptable few. This review gives a general overview of
protein tyrosine kinase structural biology, including a discussion of the strengths and limitations of the investigative methods
involved.
Received 2 May 2006; received after revision 21 June 2006; accepted 9 August 2006 相似文献
920.
Vastiau IM Anthonio EA Brams M Brees C Young SG Van de Velde S Wanders RJ Mannaerts GP Baes M Van Veldhoven PP Fransen M 《Cellular and molecular life sciences : CMLS》2006,63(14):1686-1699
Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins (PMPs), and is essential for the formation of
functional peroxisomal membranes. Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins. In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least partially farnesylated in vivo. Whether farnesylation of Pex19p plays an essential or merely ancillary role in peroxisome biogenesis is currently not clear.
Here, we show that (i) nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of PMPs,
(ii) a variant of Pex19p lacking a functional farnesylation motif is able to restore peroxisome biogenesis in Pex19p-deficient
cells, and (iii) peroxisome protein import is not affected in yeast and mammalian cells defective in one of the enzymes involved
in the farnesylation pathway. Summarized, these observations indicate that the CAAX box-mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in yeast and mammalian cells.
Received 10 March 2006; received after revision 28 April 2006; accepted 30 May 2006 相似文献