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261.
Heterotrimeric G-proteins bind to cell-surface receptors and are integral in transmission of signals from outside the cell. Upon activation of the Galpha subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and interact with effector proteins for signal transduction. Regulatory proteins with the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein subunit dissociation in the absence of Galpha activation. Here we describe the structural determinants of GoLoco activity as revealed by the crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates. The structural organization of the GoLoco Galpha(i1) complex, when combined with supporting data from domain-swapping experiments, suggests that the Galpha all-helical domain and GoLoco-region carboxy-terminal residues control the specificity of GoLoco Galpha interactions. 相似文献
262.
Biodiversity as a barrier to ecological invasion 总被引:69,自引:0,他引:69
Biological invasions are a pervasive and costly environmental problem that has been the focus of intense management and research activities over the past half century. Yet accurate predictions of community susceptibility to invasion remain elusive. The diversity resistance hypothesis, which argues that diverse communities are highly competitive and readily resist invasion, is supported by both theory and experimental studies conducted at small spatial scales. However, there is also convincing evidence that the relationship between the diversity of native and invading species is positive when measured at regional scales. Although this latter relationship may arise from extrinsic factors, such as resource heterogeneity, that covary with diversity of native and invading species at large scales, the mechanisms conferring greater invasion resistance to diverse communities at local scales remain unknown. Using neighbourhood analyses, a technique from plant competition studies, we show here that species diversity in small experimental grassland plots enhances invasion resistance by increasing crowding and species richness in localized plant neighbourhoods. Both the establishment (number of invaders) and success (proportion of invaders that are large) of invading plants are reduced. These results suggest that local biodiversity represents an important line of defence against the spread of invaders. 相似文献
263.
Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles 总被引:6,自引:0,他引:6
Protein-based hydrogels are used for many applications, ranging from food and cosmetic thickeners to support matrices for drug delivery and tissue replacement. These materials are usually prepared using proteins extracted from natural sources, which can give rise to inconsistent properties unsuitable for medical applications. Recent developments have utilized recombinant DNA methods to prepare artificial protein hydrogels with specific association mechanisms and responsiveness to various stimuli. Here we synthesize diblock copolypeptide amphiphiles containing charged and hydrophobic segments. Dilute solutions of these copolypeptides would be expected to form micelles; instead, they form hydrogels that retain their mechanical strength up to temperatures of about 90 degrees C and recover rapidly after stress. The use of synthetic materials permits adjustment of copolymer chain length and composition, which we varied to study their effect on hydrogel formation and properties. We find that gelation depends not only on the amphiphilic nature of the polypeptides, but also on chain conformations--alpha-helix, beta-strand or random coil. Indeed, shape-specific supramolecular assembly is integral to the gelation process, and provides a new class of peptide-based hydrogels with potential for applications in biotechnology. 相似文献
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Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema 总被引:16,自引:0,他引:16
Morris DG Huang X Kaminski N Wang Y Shapiro SD Dolganov G Glick A Sheppard D 《Nature》2003,422(6928):169-173
Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrin alpha(v)beta6 has another critical function; that is, it binds and activates latent transforming growth factor-beta (TGF-beta). Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)--a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema. Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12. Furthermore, we show that the effects of Itgb6 deletion are overcome by simultaneous transgenic expression of active TGF-beta1. We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression. Furthermore, we show that a functional alteration in the TGF-beta activation pathway affects susceptibility to this disease. 相似文献
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A revolution in optical manipulation 总被引:4,自引:0,他引:4
Optical tweezers use the forces exerted by a strongly focused beam of light to trap and move objects ranging in size from tens of nanometres to tens of micrometres. Since their introduction in 1986, the optical tweezer has become an important tool for research in the fields of biology, physical chemistry and soft condensed matter physics. Recent advances promise to take optical tweezers out of the laboratory and into the mainstream of manufacturing and diagnostics; they may even become consumer products. The next generation of single-beam optical traps offers revolutionary new opportunities for fundamental and applied research. 相似文献