Topic
Structural biology
About: Structural biology is a research topic. Over the lifetime, 2206 publications have been published within this topic receiving 126070 citations.
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TL;DR: The functions of proteins are critically coupled to their interplay with water, but determining the dynamics of most water molecules at protein surfaces hasn't been possible, so a new spectroscopic method promises to change that.
Abstract: The functions of proteins are critically coupled to their interplay with water, but determining the dynamics of most water molecules at protein surfaces hasn't been possible. A new spectroscopic method promises to change that.
22 citations
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TL;DR: In this paper, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and post-fusion conformations.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale (200-300 A) conformational change of the Spike protein. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein-mediated fusion, the fusion peptides must be released from the core of the protein and associate with the host membrane. While infection relies on this transition between the prefusion and postfusion conformations, there has yet to be a biophysical characterization reported for this rearrangement. That is, structures are available for the endpoints, though the intermediate conformational processes have not been described. Interestingly, the Spike protein possesses many post-translational modifications, in the form of branched glycans that flank the surface of the assembly. With the current lack of data on the pre-to-post transition, the precise role of glycans during cell invasion has also remained unclear. To provide an initial mechanistic description of the pre-to-post rearrangement, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and postfusion conformations. These simulations indicate that the steric composition of the glycans can induce a pause during the Spike protein conformational change. We additionally show that this glycan-induced delay provides a critical opportunity for the fusion peptides to capture the host cell. In contrast, in the absence of glycans, the viral particle would likely fail to enter the host. This analysis reveals how the glycosylation state can regulate infectivity, while providing a much-needed structural framework for studying the dynamics of this pervasive pathogen.
22 citations
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TL;DR: Crystal structures of proteins not only shed light on how those proteins work but can also force a re-evaluation of what other proteins are predicted to do.
Abstract: Crystal structures of proteins not only shed light on how those proteins work By revealing previously hidden similarities, they can also force a re-evaluation of what other proteins are predicted to do
22 citations
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TL;DR: A MALDI method specifically optimized for membrane protein analysis is presented here, with detailed information on the sample preparation and deposition, as well as guidelines for domain determination by limited proteolysis.
22 citations
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TL;DR: There are now several specialized mass spectrometry (MS) methods, each with unique sample preparation, data acquisition, and data processing protocols, referred to as structural MS and include cross-linking, hydrogen-deuterium exchange, hydroxyl radical footprinting, native, ion mobility, and top-down MS.
Abstract: Mass spectrometry (MS) is increasingly being used to probe the structure and dynamics of proteins and the complexes they form with other macromolecules. There are now several specialized MS methods, each with unique sample preparation, data acquisition, and data processing protocols. Collectively, these methods are referred to as structural MS and include cross-linking, hydrogen-deuterium exchange, hydroxyl radical footprinting, native, ion mobility, and top-down MS. Each of these provides a unique type of structural information, ranging from composition and stoichiometry through to residue level proximity and solvent accessibility. Structural MS has proved particularly beneficial in studying protein classes for which analysis by classic structural biology techniques proves challenging such as glycosylated or intrinsically disordered proteins. To capture the structural details for a particular system, especially larger multiprotein complexes, more than one structural MS method with other structural and biophysical techniques is often required. Key to integrating these diverse data are computational strategies and software solutions to facilitate this process. We provide a background to the structural MS methods and briefly summarize other structural methods and how these are combined with MS. We then describe current state of the art approaches for the integration of structural MS data for structural biology. We quantify how often these methods are used together and provide examples where such combinations have been fruitful. To illustrate the power of integrative approaches, we discuss progress in solving the structures of the proteasome and the nuclear pore complex. We also discuss how information from structural MS, particularly pertaining to protein dynamics, is not currently utilized in integrative workflows and how such information can provide a more accurate picture of the systems studied. We conclude by discussing new developments in the MS and computational fields that will further enable in-cell structural studies.
22 citations