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排序方式: 共有177条查询结果,搜索用时 31 毫秒
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Holdsworth G Slocombe P Doyle C Sweeney B Veverka V Le Riche K Franklin RJ Compson J Brookings D Turner J Kennedy J Garlish R Shi J Newnham L McMillan D Muzylak M Carr MD Henry AJ Ceska T Robinson MK 《The Journal of biological chemistry》2012,287(32):26464-26477
LRP5 and LRP6 are proteins predicted to contain four six-bladed β-propeller domains and both bind the bone-specific Wnt signaling antagonist sclerostin. Here, we report the crystal structure of the amino-terminal region of LRP6 and using NMR show that the ability of sclerostin to bind to this molecule is mediated by the central core of sclerostin and does not involve the amino- and carboxyl-terminal flexible arm regions. We show that this structured core region interacts with LRP5 and LRP6 via an NXI motif (found in the sequence PNAIG) within a flexible loop region (loop 2) within the central core region. This sequence is related closely to a previously identified motif in laminin that mediates its interaction with the β-propeller domain of nidogen. However, the NXI motif is not involved in the interaction of sclerostin with LRP4 (another β-propeller containing protein in the LRP family). A peptide derived from the loop 2 region of sclerostin blocked the interaction of sclerostin with LRP5/6 and also inhibited Wnt1 but not Wnt3A or Wnt9B signaling. This suggests that these Wnts interact with LRP6 in different ways. 相似文献
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PEGylated phospholipids are commonly used to increase the blood-circulation time of liposomes by providing a steric barrier around them. This paper documents a fundamentally new property of these lipids-an ability to stimulate the release of cholesterol from phospholipid membranes. Evidence for such stimulation has been obtained by measuring the transport of dehydroergosterol (DHE), a fluorescent simulant of cholesterol, from donor liposomes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG(2000)), and DHE to acceptor liposomes made from POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), and cholesterol. The potential of PEGylated lipids to serve as novel cholesterol-lowering agents is briefly discussed. 相似文献
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Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly. 相似文献
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Mehiri M Jing B Ringhoff D Janout V Cassimeris L Regen SL 《Bioconjugate chemistry》2008,19(8):1510-1513
A fluorescently labeled, persulfated molecular umbrella ( 1) has been synthesized from cholic acid, lysine, spermine, and Coumarin 343 and found capable of entering live HeLa cells. The distributions of 1 throughout the cytoplasm and the nucleus were diffuse and punctate, respectively. This finding, together with its ability to cross liposomal membranes by passive diffusion, suggests that passive diffusion plays a significant role in the ability of 1 to enter cells. The fact that 1 is concentrated at the nucleus raises the possibility that molecular umbrellas of this type could be used for the nuclear targeting of drugs. 相似文献
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Summary The Vendian-Cambrian interval on the Siberian Platform contains thick carbonate and evaporite sequences formed in extensive
shallow-water basins. The carbonate sequences are characterized by a cyclic composition. Finegrained dolomites, undulated
algal dolomites, flat pebble conglomerates, storm breccias and solution-collapse breccias form the base of each cycle. These
rocks are characterized by an increased clay content which can be high enough to form argillites. Short sedimentation breaks
reflected by mudcracks or silicification horizons are present as well as small cross-bedded tidal channels. Peloidal grainstones
with algal overgrowth dominate in the central parts of the cycles. These members are often recrystallized and dolomitized.
Micritic dolomites, undulous laminated dolomites, storm breccias and columnar stromatolites with abundant mud cracks form
the upper members of the cycles. These sequences are free of clay but contain abundant anhydrite crystals and nodules. In
the uppermost parts of some cycles massive layered anhydrite beds are present. The cycles vary in thickness, but usually they
are between 15 and 20 m thick.
The lower cycle member documents extreme shallow-water deposits. They formed in tidal and partially also supratidal zones
not far from the mainland, from where fine clayey material was washed in. These parts of the sequence reflect a slow transgression.
The central member of a cycle was deposited during the maximal transgression in a shallow basin with normal salinity and rather
active hydrodynamics.
Sedimentation of the upper part of the cycles reflects a regression stage (tidal and especially sabkha environments). The
final layered anhydrite beds formed most probably in relict lakes on the sabkha plain. During sea-level falls some sequences
of the central parts of the cycles were subaerially exposed and underwent partial dolomitization.
The Vendian-Cambrian sabkhas are partly comparable with their recent counterparts. 相似文献
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Lasioglossins LLIII affect the morphogenesis of Candida albicans and reduces the duration of experimental vaginal candidiasis in mice 下载免费PDF全文
Alena Vrablikova Lydie Czernekova Romana Cahlikova Zbynek Novy Milos Petrik Saima Imran Zdenek Novak Michal Krupka Vaclav Cerovsky Jaroslav Turanek Milan Raska 《Microbiology and immunology》2017,61(11):474-481