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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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Journal ArticleDOI
11 Jul 2019-Cell
TL;DR: This work zooming into single tagged genes using nanoscopy techniques, including an active target-locking, ultra-sensitive system that enables single-molecule detection in addressable sub-diffraction volumes, within crowded intracellular environments, sets the stage for single-Molecule studies of complex molecular processes in live cells.

103 citations

Journal ArticleDOI
TL;DR: What is known about the interaction between the chaperones and partners of Hsp70s, and HSPA8 in particular, is reviewed, with a strong slant toward structural biology.
Abstract: Hsp70 proteins are key to maintaining intracellular protein homeostasis. To carry out this task, they employ a large number of cochaperones and adapter proteins. Here, we review what is known about the interaction between the chaperones and partners, with a strong slant toward structural biology. Hsp70s in general, and Hsc70 (HSPA8) in particular, display an amazing array of interfaces with their protein cofactors. We also review the known interactions between Hsp70s with lipids and with active compounds that may become leads toward Hsp70 modulation for treatment of a variety of diseases.

102 citations

Journal ArticleDOI
09 Jul 2015-eLife
TL;DR: These structures reveal the near-identical SRP architecture of these two states, show many of the SRP-ribosome interactions at atomic resolution, and suggest how the polypeptide-binding M domain selectively engages hydrophobic signals.
Abstract: Proteins are long chain-like molecules built from smaller building blocks, called amino acids, by a large molecular machine known as a ribosome. Although all proteins are assembled inside cells, some of them must be delivered to the outside or inserted into cell membranes. It is important to understand how this selective delivery system works because secreted proteins (i.e., those delivered outside) and membrane-embedded proteins are essential for cells to communicate with their surroundings. Proteins destined for secretion or membrane insertion contain characteristic stretches of amino acids that act as a targeting signal for delivery to the membrane. These targeting signals are recognized by the ‘signal recognition particle’ (or SRP for short), a large complex found in all living organisms. The SRP has the task of finding ribosomes that are assembling proteins with a targeting signal, and then taking them to the membrane. The protein being assembled can then either cross the membrane for secretion by the cell, or get embedded within the membrane. So, how can the SRP scan the broad range of proteins that are made by the ribosome and engage with only those containing targeting signals? Voorhees and Hegde investigated this question by analyzing SRPs bound to ribosomes that were at different stages of building a membrane protein. The experiment was devised so that SRP would be in two different states: in the first state, the SRP was scanning for its targeting signal and, in the second, it was engaged with the targeting signal. Voorhees and Hegde took many thousands of pictures of these samples using a technique called cryo-electron microscopy, and reconstructed the three-dimensional structures of both states. This revealed fine details of how SRP positions itself immediately next to the part of the ribosome where newly formed protein chains emerge. From here, the SRP scans the protein until the targeting signal emerges and then it engages with the protein. Engaging the targeting signal just as it emerges from the ribosome is probably important because targeting signals tend to aggregate if they are exposed to the contents of a cell. The new structures show how SRP cradles the targeting signal inside a binding groove and covers it with a protective lid to minimize its risk of aggregation. The next challenges are to figure out how SRP chooses which ribosomes to scan, and how it releases the targeting signal when it has delivered it to the membrane.

102 citations

Journal ArticleDOI
TL;DR: The host defense functions of the C-reactive protein using transgenic mice infected with Streptococcus pneumoniae had increased lifespan and lowered mortality compared to wild-type mice and a complement-independent host protective effect was also demonstrated.
Abstract: Human C-reactive protein is a Ca2+-binding acute phase-protein with binding specificity for phosphocholine. Recent crystallographic and mutagenesis studies have provided a solid understanding of the structural biology of the protein, while experiments using transgenic mice have confirmed its host-defense function. The protein consists of five identical protomers in cyclic symmetry. On one face of each protomer there is a binding site for phosphocholine consisting of two Ca2+ ions that ligate the phosphate group and a hydrophobic pocket that accommodates the methyl groups of phosphocholine. On the opposite face is a deep cleft formed by parts of the N and C termini and bordered by an alpha-helix. Mutational studies indicate that the C1q-binding site of the molecule is located at the open end of this cleft with Asp112 and Tyr175 representing contact residues. Using human C-reactive protein transgenic mice, we investigated the host defense functions of the protein. Transgenic mice infected with Streptococcus pneumoniae had increased lifespan and lowered mortality compared to wild-type mice. This was attributable to an up to 400-fold reduction in bacteremia mediated mainly by the interaction of C-reactive protein with complement. A complement-independent host protective effect was also demonstrated.

102 citations

Journal ArticleDOI
15 Aug 2018-eLife
TL;DR: The peptidisc method is rapid and cost-effective, and it may emerge as a universal tool for high-throughput stabilization of membrane proteins to advance modern biological studies.
Abstract: Membrane proteins are difficult to work with due to their insolubility in aqueous solution and quite often their poor stability in detergent micelles. Here, we present the peptidisc for their facile capture into water-soluble particles. Unlike the nanodisc, which requires scaffold proteins of different lengths and precise amounts of matching lipids, reconstitution of detergent solubilized proteins in peptidisc only requires a short amphipathic bi-helical peptide (NSPr) and no extra lipids. Multiple copies of the peptide wrap around to shield the membrane-exposed part of the target protein. We demonstrate the effectiveness of this 'one size fits all' method using five different membrane protein assemblies (MalFGK2, FhuA, SecYEG, OmpF, BRC) during 'on-column', 'in-gel', and 'on-bead' reconstitution embedded within the membrane protein purification protocol. The peptidisc method is rapid and cost-effective, and it may emerge as a universal tool for high-throughput stabilization of membrane proteins to advance modern biological studies.

101 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202335
202272
2021149
2020154
2019152
2018140