Alber, F. et al. Determining the architectures of macromolecular assemblies. Nature 450, 683-694

Department of Bioengineering and Therapeutic Sciences, and California Institute for Quantitative Biosciences, Byers Hall, Suite 503B, 1700 4th Street, University of California at San Francisco, San Francisco, California 94158-2330, USA.
Nature (Impact Factor: 42.35). 12/2007; 450(7170):683-94. DOI: 10.1038/nature06404
Source: PubMed

ABSTRACT To understand the workings of a living cell, we need to know the architectures of its macromolecular assemblies. Here we show how proteomic data can be used to determine such structures. The process involves the collection of sufficient and diverse high-quality data, translation of these data into spatial restraints, and an optimization that uses the restraints to generate an ensemble of structures consistent with the data. Analysis of the ensemble produces a detailed architectural map of the assembly. We developed our approach on a challenging model system, the nuclear pore complex (NPC). The NPC acts as a dynamic barrier, controlling access to and from the nucleus, and in yeast is a 50 MDa assembly of 456 proteins. The resulting structure, presented in an accompanying paper, reveals the configuration of the proteins in the NPC, providing insights into its evolution and architectural principles. The present approach should be applicable to many other macromolecular assemblies.

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Available from: Michael P Rout, Sep 03, 2015
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    • "Proteomic and microscopic analysis have deciphered that the entire NPC is comprised of distinct subcomplexes that are octagonally arranged around a central channel (Cronshaw et al., 2002; Alber et al., 2007a, b; Fiserova et al., 2009; Degrasse and Devos, 2010; Tamura et al., 2010). The size of a single NPC varies between ~60 MDa in yeast and ~120 MDa in metazoans but contain similar sets of core proteins. "
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    ABSTRACT: The nuclear pore complex (NPC) is a multisubunit protein conglomerate that facilitates movement of RNA and protein between the nucleus and cytoplasm. Relatively little is known regarding the influence of the Arabidopsis NPC on growth and development. Seedling development, flowering time, nuclear morphology, mRNA accumulation, and gene expression changes in Arabidopsis nucleoporin mutants were investigated. Nuclear export of mRNA is differentially affected in plants with defects in nucleoporins that lie in different NPC subcomplexes. This study reveals differences in the manner by which nucleoporins alter molecular and plant growth phenotypes, suggesting that nuclear pore subcomplexes play distinct roles in nuclear transport and reveal a possible feedback relationship between the expression of genes involved in nuclear transport.
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    • "Transport phenomena involving diffusion are commonly encountered in nature [1] [2], in various technological processes [3] [4] and biological systems [5] [6], and thus have been thoroughly studied. Most of the research has focused on the macroscale , where fundamental laws, such as Fick's or Darcy's law, describe movement of a given substance through a medium. "
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    Computer Methods in Applied Mechanics and Engineering 02/2014; 269:123–138. DOI:10.1016/j.cma.2013.11.010 · 2.63 Impact Factor
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    • "Many complex traits are also described as irreducible, because the absence of any component of such a trait would abolish its overall function (Weber, 1999). Although complex traits are omnipresent in life at different biological scales, with examples ranging from butterfly wing patterning to the assembly of multiprotein complexes (Beldade & Brakefield, 2002; Alber et al., 2007), little is known about the stepwise trajectories through which complex traits arise in nature. Charles Darwin pondered this question in the Origin of Species using the evolution of the complex human eye as an example, writing, 'To suppose that the eye … could have been formed by natural selection, seems, I freely confess, absurd in the highest possible degree.' "
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