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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: The outlook of the "holy grail" of understanding in atomic detail the diverse functions of TRP channels is summarized by summarizing the outlook from electron microscopy, X-ray crystallography, and nuclear magnetic resonance of the resulting insights into TRP channel function.
Abstract: Membrane proteins remain challenging targets for structural biologists, despite recent technical developments regarding sample preparation and structure determination. We review recent progress towards a structural understanding of TRP channels and the techniques used to that end. We discuss available low-resolution structures from electron microscopy (EM), X-ray crystallography, and nuclear magnetic resonance (NMR) and review the resulting insights into TRP channel function for various subfamily members. The recent high-resolution structure of TRPV1 is discussed in more detail in Chapter 11. We also consider the opportunities and challenges of using the accumulating structural information on TRPs and homologous proteins for deducing full-length structures of different TRP channel subfamilies, such as building homology models. Finally, we close by summarizing the outlook of the "holy grail" of understanding in atomic detail the diverse functions of TRP channels.
60 citations
TL;DR: The findings indicate the establishment of a biosynthetic route for producing large amounts of sumoylated recombinant proteins that will open up new avenues for studying the biochemical and structural aspects of the SUMO‐1 modification pathway.
60 citations
TL;DR: A recently developed general method for determining the structures of unmodified membrane proteins in phospholipid bilayers by solid-state NMR spectroscopy, which elaborates on oriented sample (OS) solid- state NMR, its complementary predecessor.
Abstract: One of the most important topics in experimental structural biology is determining the structures of membrane proteins. These structures represent one-third of all of the information expressed from a genome, distinguished by their locations within the phospholipid bilayer of cells, organelles, or enveloped viruses. Their highly hydrophobic nature and insolubility in aqueous media means that they require an amphipathic environment. They have unique functions in transport, catalysis, channel formation, and signaling. Researchers are particularly interested in G-protein coupled receptors (GPCRs) because they modulate many biological processes, and about half of the approximately 800 of these proteins within the human genome are or can be turned into drug receptors that affect a wide range of diseases. Because of experimental difficulties, researchers have studied membrane proteins using a wide variety of artificial media that mimic membranes, such as mixed organic solvents or detergents. More sophisticated mimics include bilayer discs (bicelles) and the lipid cubic phase (LCP), but both of these contain a very large detergent component, which can disrupt the stability and function of membrane proteins. To have confidence in the resulting structures and their biological functions and to avoid disrupting these delicate proteins, the structures of membrane proteins should be determined in their native environment of liquid crystalline phospholipid bilayers under physiological conditions. This Account describes a recently developed general method for determining the structures of unmodified membrane proteins in phospholipid bilayers by solid-state NMR spectroscopy. Because it relies on the natural, rapid rotational diffusion of these proteins about the bilayer normal, this method is referred to as rotationally aligned (RA) solid-state NMR. This technique elaborates on oriented sample (OS) solid-state NMR, its complementary predecessor. These methods exploit the power of solid-state NMR, which enables researchers to obtain well-resolved spectra from "immobile" membrane proteins in phospholipid bilayers, to separate and measure frequencies that reflect orientations with respect to the bilayer normal, and to make complementary distance measurements. The determination of the structures of several membrane proteins, most prominently the chemokine receptor CXCR1, a 350-residue GPCR, has demonstrated this approach.
59 citations
TL;DR: The results of a double‐blind study are presented in which a new ab initio method was successfully used to predict the 3D structure of a protein designed through an experimental approach using binary patterned combinatorial libraries of de novo sequences.
Abstract: Ab initio structure prediction and de novo protein design are two problems at the forefront of research in the fields of structural biology and chemistry. The goal of ab initio structure prediction of proteins is to correctly characterize the 3D structure of a protein using only the amino acid sequence as input. De novo protein design involves the production of novel protein sequences that adopt a desired fold. In this work, the results of a double-blind study are presented in which a new ab initio method was successfully used to predict the 3D structure of a protein designed through an experimental approach using binary patterned combinatorial libraries of de novo sequences. The predicted structure, which was produced before the experimental structure was known and without consideration of the design goals, and the final NMR analysis both characterize this protein as a 4-helix bundle. The similarity of these structures is evidenced by both small RMSD values between the coordinates of the two structures and a detailed analysis of the helical packing.
59 citations
TL;DR: A number of applications to selected fibrils, including prions, α-synuclein and Amyloid-β (Aβ), are discussed, including the latter is, as for its small monomer size, accessible to full 3D structure determination by solid-state NMR.
59 citations