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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: Here it is considered in detail the diverse strategies that viruses have evolved to target and subvert NPCs during infection.
27 citations
TL;DR: The structure of the single-stranded overhang is not known with certainty, with disparate models proposed in the literature as discussed by the authors, and the results of an integrated structural biology approach that combines small-angle X-ray scattering, circular dichroism (CD), analytical ultracentrifugation, size-exclusion column chromatography and molecular dynamics simulations that provide the most detailed characterization to date of the structure of telomeric overhang.
Abstract: Human telomeres contain the repeat DNA sequence 5'-d(TTAGGG), with duplex regions that are several kilobases long terminating in a 3' single-stranded overhang. The structure of the single-stranded overhang is not known with certainty, with disparate models proposed in the literature. We report here the results of an integrated structural biology approach that combines small-angle X-ray scattering, circular dichroism (CD), analytical ultracentrifugation, size-exclusion column chromatography and molecular dynamics simulations that provide the most detailed characterization to date of the structure of the telomeric overhang. We find that the single-stranded sequences 5'-d(TTAGGG)n, with n = 8, 12 and 16, fold into multimeric structures containing the maximal number (2, 3 and 4, respectively) of contiguous G4 units with no long gaps between units. The G4 units are a mixture of hybrid-1 and hybrid-2 conformers. In the multimeric structures, G4 units interact, at least transiently, at the interfaces between units to produce distinctive CD signatures. Global fitting of our hydrodynamic and scattering data to a worm-like chain (WLC) model indicates that these multimeric G4 structures are semi-flexible, with a persistence length of ∼34 A. Investigations of its flexibility using MD simulations reveal stacking, unstacking, and coiling movements, which yield unique sites for drug targeting.
26 citations
TL;DR: High resolution structures have recently been determined for the TatA and TatC proteins that form the Tat translocation site, and these structures provide a molecular framework for understanding the mechanism of Tat transport.
26 citations
TL;DR: It is discovered that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity.
Abstract: Many proteins need to interact with other proteins to carry out their various tasks in cells. Such interactions are essential for almost all biological processes and are often disrupted in disease. Cells have thousands of different types of proteins and each has a unique shape that determines which other proteins it can bind to. It was previously thought that two proteins bind to each other in a manner similar to that of a lock and a key, in which the rigid shape of one protein meshes perfectly with the rigid shape of its partner. However, many proteins are flexible and adopt different shapes depending on whether they are attached to their partner, or not. Moreover, an individual protein may also bind to several different partners, each requiring that protein to adopt several different shapes. These observations have challenged the lock and key model and suggest that flexibility in the structure of a protein plays a key role in its binding to other proteins. However, it is not clear how structural flexibility enables a protein to bind to several different partners while being selective enough to prevent the protein from binding to the wrong ones. A protein called PD-1 is involved in immune responses in humans and is an emerging target for drugs to treat cancer. Pabon and Camacho used computer simulations to model PD-1’s structural flexibility and to find out how this enables the protein to form different shapes when it binds to different partners. The experiments show that the region of PD-1 that binds to other proteins adopts a different shape in the absence and presence of its partners. The binding partners make initial contact with PD-1 via specific features that they share in common. This causes PD-1 to change shape, uncovering a surface of PD-1 that is flexible and is able to accommodate a variety of partners. After this, the binding partners form additional contacts with PD-1 that are specific to each partner. These findings suggest that the ability of a protein to bind to several different partners is unlocked by certain structures that are present in the binding partners. These structures are found in proteins produced by many different organisms, suggesting that this mechanism is likely to be widespread in nature. This work may open up new avenues for designing drugs to target PD-1 and other proteins that contribute to disease but have so far been impossible to target with drugs.
26 citations
TL;DR: This review focuses on recent advances in the field of protein folding and discusses possible links between folding, stability, and binding dynamics.
26 citations