Current Opinion in Structural Biology

Linking structural change with functional regulation-insights from mass spectrometry.

Publication Date: 2012 Jan 31 PMID: 22300497
Authors: Morgner, N. - Robinson, C. V.
Journal: Curr Opin Struct Biol

A wide range of biophysical approaches has been applied to structural biology, all with the same overall goal-to understand the molecular machines that allow cells to function. While knowledge of the identity and composition of component protein subunits is an important foundation for understanding these macromolecular complexes it has become increasingly clear that knowledge of the exact composition alone is insufficient for understanding dynamic interactions and regulatory mechanisms. In this review we focus on recent developments of mass spectrometry (MS) that allow us to unravel the functional 'secrets' of non-covalent molecular machines.

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Towards a molecular view of transcriptional control.

Publication Date: 2012 Jan 30 PMID: 22296921
Authors: Zakrzewska, K. - Lavery, R.
Journal: Curr Opin Struct Biol

The accumulation of experimental data over recent years has fueled theoretical work on how transcription factors (TFs) search for and recognise their DNA target sites, how they interact with one another, or with other DNA-binding proteins, and how they cope with the compaction of DNA within bacterial nucleoids or within eukaryotic chromatin. Many models have been built to study the kinetic, thermodynamic and mechanistic aspects of these questions. In some cases they have resulted in a relatively clear consensus view, but a number of questions remain controversial. We present an overview of recent work, with an emphasis on models that provide, or can inspire, a better understanding of transcriptional control at a detailed molecular level.

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Nucleic acid packaging in viruses.

Publication Date: 2012 Jan 23 PMID: 22277169
Authors: Speir, J. A. - Johnson, J. E.
Journal: Curr Opin Struct Biol

We review recent literature describing protein nucleic acid interactions and nucleic acid organization in viruses. The nature of the viral genome determines its overall organization and its interactions with the capsid protein. Genomes composed of single strand (ss) RNA and DNA are highly flexible and, in some cases, adapt to the symmetry of the particle-forming protein to show repeated, sequence independent, nucleoprotein interactions. Genomes composed of double-stranded (ds) DNA do not interact strongly with the container due to their intrinsic stiffness, but form well-organized layers in virions. Assembly of virions with ssDNA and ssRNA genomes usually occurs through a cooperative condensation of the protein and genome, while dsDNA viruses usually pump the genome into a preformed capsid with a strong, virally encoded, molecular motor complex. We present data that suggest the packing density of ss genomes and ds genomes are comparable, but the latter exhibit far higher pressures due to their stiffness.

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Coarse-graining of multiprotein assemblies.

Publication Date: 2012 Jan 23 PMID: 22277168
Authors: Saunders, M. G. - Voth, G. A.
Journal: Curr Opin Struct Biol

Multiscale models are important tools to elucidate how small changes in local subunit conformations may propagate to affect the properties of macromolecular complexes. We review recent advances in coarse-graining methods for poly-protein assemblies, systems that are composed of many copies of relatively few components, with a particular focus on viral capsids and cytoskeletal filaments. These methods are grouped into two broad categories-mapping methods, which use information from one scale of representation to parameterize a lower resolution model, and bridging methods, which repeatedly connect different scales during simulation-and we provide examples of both classes at different levels of complexity. Collectively, these models illustrate the numerous approaches to information transfer between scales and demonstrate that the complexity required of the model depends in general on the nature of the information sought.

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Folding and binding: lingering questions, emerging answers.

Publication Date: 2012 Jan 19 PMID: 22265341
Authors: Itzhaki, L. S. - Rose, G. D.
Journal: Curr Opin Struct Biol

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Proteins for packaging, partitioning, processing, and proofing of nucleic acids.

Publication Date: 2012 Jan 17 PMID: 22261637
Authors: Phillips, S. E. - Luger, K.
Journal: Curr Opin Struct Biol

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Atomistic molecular simulations of protein folding.

Publication Date: 2012 Jan 16 PMID: 22257762
Authors: Best, R. B.
Journal: Curr Opin Struct Biol

Theory and experiment have provided answers to many of the fundamental questions of protein folding; a remaining challenge is an accurate, high-resolution picture of folding mechanism. Atomistic molecular simulations with explicit solvent are the most promising method for providing this information, by accounting more directly for the physical interactions that stabilize proteins. Although simulations of folding with such force fields are extremely challenging, they have become feasible as a result of recent advances in computational power, accuracy of the energy functions or 'force fields', and methods for improving sampling of folding events. I review the recent progress in these areas, and highlight future challenges and questions that we may hope to address with these methods. I also attempt to place atomistic models into the context of the energy landscape view of protein folding, and coarse-grained simulations.

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Damage recognition in nucleotide excision DNA repair.

Publication Date: 2012 Jan 16 PMID: 22257761
Authors: Kuper, J. - Kisker, C.
Journal: Curr Opin Struct Biol

Nucleotide excision repair (NER) is a highly versatile DNA repair process. Its ability to repair a large number of different damages with the same subset of recognition factors requires structural tools for damage recognition that are both broad and very accurate. Over the past few years detailed structural information on damage recognition factors from eukaryotic and prokaryotic NER has emerged. These structures shed light on the toolkit utilized in the damage recognition process and help explain the broad substrate specificity of NER.

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