排序方式: 共有43条查询结果,搜索用时 15 毫秒
41.
Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA 总被引:34,自引:0,他引:34
DNA mismatch repair is critical for increasing replication fidelity in organisms ranging from bacteria to humans. MutS protein, a member of the ABC ATPase superfamily, recognizes mispaired and unpaired bases in duplex DNA and initiates mismatch repair. Mutations in human MutS genes cause a predisposition to hereditary nonpolyposis colorectal cancer as well as sporadic tumours. Here we report the crystal structures of a MutS protein and a complex of MutS with a heteroduplex DNA containing an unpaired base. The structures reveal the general architecture of members of the MutS family, an induced-fit mechanism of recognition between four domains of a MutS dimer and a heteroduplex kinked at the mismatch, a composite ATPase active site composed of residues from both MutS subunits, and a transmitter region connecting the mismatch-binding and ATPase domains. The crystal structures also provide a molecular framework for understanding hereditary nonpolyposis colorectal cancer mutations and for postulating testable roles of MutS. 相似文献
42.
Chen ST Lin YL Huang MT Wu MF Cheng SC Lei HY Lee CK Chiou TW Wong CH Hsieh SL 《Nature》2008,453(7195):672-676
Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts. CLEC5A (C-type lectin domain family 5, member A; also known as myeloid DAP12-associating lectin (MDL-1)) contains a C-type lectin-like fold similar to the natural-killer T-cell C-type lectin domains and associates with a 12-kDa DNAX-activating protein (DAP12) on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation. The CLEC5A-DV interaction does not result in viral entry but stimulates the release of proinflammatory cytokines. Blockade of CLEC5A-DV interaction suppresses the secretion of proinflammatory cytokines without affecting the release of interferon-alpha, supporting the notion that CLEC5A acts as a signalling receptor for proinflammatory cytokine release. Moreover, anti-CLEC5A monoclonal antibodies inhibit DV-induced plasma leakage, as well as subcutaneous and vital-organ haemorrhaging, and reduce the mortality of DV infection by about 50% in STAT1-deficient mice. Our observation that blockade of CLEC5A-mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with DV (either alone or complexed with an enhancing antibody) offers a promising strategy for alleviating tissue damage and increasing the survival of patients suffering from dengue haemorrhagic fever and dengue shock syndrome, and possibly even other virus-induced inflammatory diseases. 相似文献
43.
Dadson SJ Hovius N Chen H Dade WB Hsieh ML Willett SD Hu JC Horng MJ Chen MC Stark CP Lague D Lin JC 《Nature》2003,426(6967):648-651
The erosion of mountain belts controls their topographic and structural evolution and is the main source of sediment delivered to the oceans. Mountain erosion rates have been estimated from current relief and precipitation, but a more complete evaluation of the controls on erosion rates requires detailed measurements across a range of timescales. Here we report erosion rates in the Taiwan mountains estimated from modern river sediment loads, Holocene river incision and thermochronometry on a million-year scale. Estimated erosion rates within the actively deforming mountains are high (3-6 mm yr(-1)) on all timescales, but the pattern of erosion has changed over time in response to the migration of localized tectonic deformation. Modern, decadal-scale erosion rates correlate with historical seismicity and storm-driven runoff variability. The highest erosion rates are found where rapid deformation, high storm frequency and weak substrates coincide, despite low topographic relief. 相似文献