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Structure of the ESCRT-II endosomal trafficking complex   总被引:1,自引:0,他引:1  
Hierro A  Sun J  Rusnak AS  Kim J  Prag G  Emr SD  Hurley JH 《Nature》2004,431(7005):221-225
The multivesicular-body (MVB) pathway delivers transmembrane proteins and lipids to the lumen of the endosome. The multivesicular-body sorting pathway has crucial roles in growth-factor-receptor downregulation, developmental signalling, regulation of the immune response and the budding of certain enveloped viruses such as human immunodeficiency virus. Ubiquitination is a signal for sorting into the MVB pathway, which also requires the functions of three protein complexes, termed ESCRT-I, -II and -III (endosomal sorting complex required for transport). Here we report the crystal structure of the core of the yeast ESCRT-II complex, which contains one molecule of the Vps protein Vps22, the carboxy-terminal domain of Vps36 and two molecules of Vps25, and has the shape of a capital letter 'Y'. The amino-terminal coiled coil of Vps22 and the flexible linker leading to the ubiquitin-binding NZF domain of Vps36 both protrude from the tip of one branch of the 'Y'. Vps22 and Vps36 form nearly equivalent interactions with the two Vps25 molecules at the centre of the 'Y'. The structure suggests how ubiquitinated cargo could be passed between ESCRT components of the MVB pathway through the sequential transfer of ubiquitinated cargo from one complex to the next.  相似文献   
2.
This paper proposes that the gradual alteration of the predominant epistemic paradigm in crustal seismology in the interwar period—namely, simplicity—came about because of the strong influence of a particular commercial environment, i.e. the oil industry. I begin by demonstrating the interwar predominance of Jeffreys’ ‘simplicity postulate’ and his probabilistic epistemology, highlighting the espousal by several seismologists (Bullen, Stoneley, Byerly), whose crustal models drew on mathematical idealisations. Next, I demonstrate that the renunciation of simplicity in the 1930s came about too quickly, and, above all, too heterodoxically to have been the result of new geological evidence. Rather, I argue, the paradigm shift among seismologists was a result of the significant rise in seismic exploration generated by the oil industry. Driven by market demands, American petroleum companies pioneered new technologies, organised research initiatives, and trained young geophysicists who, through the fusion of experimentalism and field experience, brought about fundamental progress in earthquake seismology. Remarkably, historians of science have almost entirely failed to recognise the interwar primacy of the simplicity paradigm as well as its subsequent renunciation. More importantly, they have failed to acknowledge the role the oil industry played in contributing to this renunciation and to the development of new paradigms in seismology.  相似文献   
3.
The retromer complex is required for the sorting of acid hydrolases to lysosomes, transcytosis of the polymeric immunoglobulin receptor, Wnt gradient formation, iron transporter recycling and processing of the amyloid precursor protein. Human retromer consists of two smaller complexes: the cargo recognition VPS26-VPS29-VPS35 heterotrimer and a membrane-targeting heterodimer or homodimer of SNX1 and/or SNX2 (ref. 13). Here we report the crystal structure of a VPS29-VPS35 subcomplex showing how the metallophosphoesterase-fold subunit VPS29 (refs 14, 15) acts as a scaffold for the carboxy-terminal half of VPS35. VPS35 forms a horseshoe-shaped, right-handed, alpha-helical solenoid, the concave face of which completely covers the metal-binding site of VPS29, whereas the convex face exposes a series of hydrophobic interhelical grooves. Electron microscopy shows that the intact VPS26-VPS29-VPS35 complex is a stick-shaped, flexible structure, approximately 21 nm long. A hybrid structural model derived from crystal structures, electron microscopy, interaction studies and bioinformatics shows that the alpha-solenoid fold extends the full length of VPS35, and that VPS26 is bound at the opposite end from VPS29. This extended structure presents multiple binding sites for the SNX complex and receptor cargo, and appears capable of flexing to conform to curved vesicular membranes.  相似文献   
4.
Sydney Chapman is unanimously considered to have played a founding role in modern geomagnetism and to have opened up new lines of research in geophysics generally. Nevertheless, Chapman's conviction regarding the synthesis of the explanatory mechanisms of the atmosphere has gone practically unnoticed in the historiography of geophysics. This paper examines Chapman's contribution to ionospheric physics. It aims to understand Chapman's theory of ionospheric layer formation, and particularly its link to his theory of ozone formation. It deals first with the traits which characterized Chapman's personality, as a way of explaining—and even perhaps justifying— his quest for the integration and synthesis of geophysical knowledge. It then analyses Chapman's model of ionospheric layers and his suggestions regarding its use as an operational tool (without ontological connotations), before continuing with his account of the formation of the ozone layer, which seemed to constitute the missing link for understanding ionosphere layer formation. The paper concludes with Chapman's attempt to reconcile geomagnetic and radio evidence.  相似文献   
5.
This paper uses high‐frequency continuous intraday electricity price data from the EPEX market to estimate and forecast realized volatility. Three different jump tests are used to break down the variation into jump and continuous components using quadratic variation theory. Several heterogeneous autoregressive models are then estimated for the logarithmic and standard deviation transformations. Generalized autoregressive conditional heteroskedasticity (GARCH) structures are included in the error terms of the models when evidence of conditional heteroskedasticity is found. Model selection is based on various out‐of‐sample criteria. Results show that decomposition of realized volatility is important for forecasting and that the decision whether to include GARCH‐type innovations might depend on the transformation selected. Finally, results are sensitive to the jump test used in the case of the standard deviation transformation.  相似文献   
6.
In 1865, Spanish Jesuits founded the Manila Observatory, the earliest of the Far East centres devoted to typhoon and earthquake studies. Also on Philippine soil and under the direction of the Jesuits, in 1884 the Madrid government inaugurated the first Meteorological Service in the Spanish Kingdom, and most probably in the Far East. Nevertheless, these achievements not only went practically unnoticed in the historiography of science, but neither does the process of geophysical dissemination that unfolded fit in with the two types of transmitter of knowledge identified by historians in the missionary diffusion of the exact sciences in colonial contexts. Rather than regarding science as merely a stimulus to their functionary and missionary tasks, Spanish Jesuits used their overseas posting to produce and publish original research –– a feature that would place them within the typology of the ‘seeker’ rather than the ‘functionary’ (in stark contrast to what the standard typology sustains). This paper also analyses examples of synergies between science, education and trade, which denotes, inter alia, the existence of a broad and solid educational structure in the Manila Mission that sustained the strength of research enterprise.  相似文献   
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