The structural dynamics of macromolecular processes

Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, 1700 4th Street, San Francisco, CA 94158-2330, USA.
Current opinion in cell biology (Impact Factor: 8.47). 03/2009; 21(1):97-108. DOI: 10.1016/
Source: PubMed


Dynamic processes involving macromolecular complexes are essential to cell function. These processes take place over a wide variety of length scales from nanometers to micrometers, and over time scales from nanoseconds to minutes. As a result, information from a variety of different experimental and computational approaches is required. We review the relevant sources of information and introduce a framework for integrating the data to produce representations of dynamic processes.

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    • "The molecular architecture of INO80 was determined with a 17-A ˚ resolution cryo-electron microscopy (EM) map and 212 intra-protein and 116 inter-protein crosslinks (Russel et al., 2009). The molecular architecture of Polycomb Repressive Complex 2 (PRC2) was determined with a 21-A ˚ resolution negative-stain EM map and 60 intra-protein and inter-protein crosslinks (Shi et al., 2014). "
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    ABSTRACT: Structures of biomolecular systems are increasingly computed by integrative modeling that relies on varied types of experimental data and theoretical information. We describe here the proceedings and conclusions from the first wwPDB Hybrid/Integrative Methods Task Force Workshop held at the European Bioinformatics Institute in Hinxton, UK, on October 6 and 7, 2014. At the workshop, experts in various experimental fields of structural biology, experts in integrative modeling and visualization, and experts in data archiving addressed a series of questions central to the future of structural biology. How should integrative models be represented? How should the data and integrative models be validated? What data should be archived? How should the data and models be archived? What information should accompany the publication of integrative models? Copyright © 2015 Elsevier Ltd. All rights reserved.
    Structure 06/2015; 23(7). DOI:10.1016/j.str.2015.05.013 · 5.62 Impact Factor
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    • "In general, epitope tags provide a static snapshot of proteins in the cell. However, most proteins are dynamic, and this is often an important aspect of their function (Russel et al. 2009; Hinkson and Elias 2011). "
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    ABSTRACT: Proteins are not static entities. They are highly mobile and their steady state levels are achieved by a balance between ongoing synthesis and degradation. The dynamic properties of a protein can have important consequences for its function. For example, when a protein is degraded and replaced by a newly synthesized one, post-translational modifications are lost and need to be reincorporated in the new molecules. Protein stability and mobility are also relevant for duplication of macromolecular structures or organelles, which involves coordination of protein inheritance with the synthesis and assembly of newly synthesized proteins. To measure protein dynamics we recently developed a genetic pulse-chase assay called Recombination-Induced Tag Exchange (RITE). RITE has been successfully used in Saccharomyces cerevisiae to measure turnover and inheritance of histone proteins, to study changes in post-translational modifications on aging proteins, and to visualize the spatiotemporal inheritance of protein complexes and organelles in dividing cells. Here we describe a series of successful RITE cassettes that are designed for biochemical analyses, genomics studies, as well as single cell fluorescence applications. Importantly, the genetic nature and the stability of the tag-switch offer the unique possibility to combine RITE with high-throughput screening for protein dynamics mutants and mechanisms. The RITE cassettes are widely applicable, modular by design, and can therefore be easily adapted for use in other cell types or organisms.
    G3-Genes Genomes Genetics 05/2013; 3(8). DOI:10.1534/g3.113.006213 · 3.20 Impact Factor
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    • "Over the past two decades native MS has evolved to become a structural biology approach of remarkably general utility, providing insights into the composition, architecture, and dynamics of protein complexes. With the realization that the study of the most challenging systems is likely to require a combination of approaches [199,200] and an appreciation of the cellular environment [192], MS will have a crucial role in characterizing the molecular structure, dynamics, and interactions of molecules in the cell. "
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    ABSTRACT: Mass spectrometry (MS) is a recognized approach for characterizing proteins and the complexes they assemble into. This application of a long-established physico-chemical tool to the frontiers of structural biology has stemmed from experiments performed in the early 1990s. While initial studies focused on the elucidation of stoichiometry by means of simple mass determination, developments in MS technology and methodology now allow researchers to address questions of shape, inter-subunit connectivity and protein dynamics. Here, we chart the remarkable rise of MS and its application to biomolecular complexes over the last two decades.
    Journal of The Royal Society Interface 02/2012; 9(70):801-16. DOI:10.1098/rsif.2011.0823 · 3.92 Impact Factor
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