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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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    • "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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    • "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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