Institution
Laboratory of Molecular Biology
Facility•Cambridge, Cambridgeshire, United Kingdom•
About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.
Topics: Gene, RNA, DNA, Population, Receptor
Papers published on a yearly basis
Papers
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TL;DR: New evidence suggests that some PHD fingers bind to nucleosomes, raising the possibility that chromatin might be a common nuclear ligand ofPHD fingers.
401 citations
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TL;DR: In this review, it is suggested that there might be over a million instances of peptide motifs in the human proteome, a staggering number that suggests that peptides are numerous and the most understudied functional module in the cell.
400 citations
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TL;DR: It is shown that loss of cytosine-5 methylation in vault RNAs causes aberrant processing into Argonaute-associated small RNA fragments that can function as microRNAs, and impaired processing of vault ncRNA may contribute to the etiology of NSun2-deficiency human disorders.
400 citations
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TL;DR: A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies and accounts for the greater seeding potency of brain aggregates.
Abstract: A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies. This ordered assembly causes disease and represents the gain of toxic function. In recent years, evidence has accumulated to suggest that Tau inclusions form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of pathology is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighboring cells. In mice, the intracerebral injection of Tau inclusions induces the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Conformational differences between Tau aggregates from transgenic mouse brain and in vitro assembled recombinant protein account for the greater seeding potency of brain aggregates. Short fibrils constitute the major species of seed-competent Tau in the brains of transgenic mice. The existence of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.
400 citations
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TL;DR: A model is proposed in which sterol and membrane binding promote reciprocal conformational changes that facilitate a sterol transfer and signalling cycle and shows that sterol binding closes the lid and stabilizes a conformation favouring transport across aqueous barriers and signal transmission.
Abstract: The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans1,2, and are implicated in the regulation of sterol homeostasis3,4 and in signal transduction pathways5. Here we report the structure of the full-length yeast ORP Osh4 (also known as Kes1) at 1.5–1.9 A resolution in complexes with ergosterol, cholesterol, and 7-, 20- and 25-hydroxycholesterol. We find that a single sterol molecule binds within a hydrophobic tunnel in a manner consistent with a transport function for ORPs. The entrance is blocked by a flexible amino-terminal lid and surrounded by basic residues that are critical for Osh4 function. The structure of the open state of a lid-truncated form of Osh4 was determined at 2.5 A resolution. Structural analysis and limited proteolysis show that sterol binding closes the lid and stabilizes a conformation favouring transport across aqueous barriers and signal transmission. The structure of Osh4 in the absence of ligand exposes potential phospholipid-binding sites that are positioned for membrane docking and sterol exchange. On the basis of these observations, we propose a model in which sterol and membrane binding promote reciprocal conformational changes that facilitate a sterol transfer and signalling cycle.
399 citations
Authors
Showing all 19431 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert J. Lefkowitz | 214 | 860 | 147995 |
Ronald M. Evans | 199 | 708 | 166722 |
Tony Hunter | 175 | 593 | 124726 |
Marc G. Caron | 173 | 674 | 99802 |
Mark Gerstein | 168 | 751 | 149578 |
Timothy A. Springer | 167 | 669 | 122421 |
Harvey F. Lodish | 165 | 782 | 101124 |
Ira Pastan | 160 | 1286 | 110069 |
Bruce N. Ames | 158 | 506 | 129010 |
Philip Cohen | 154 | 555 | 110856 |
Gerald M. Rubin | 152 | 382 | 115248 |
Ashok Kumar | 151 | 5654 | 164086 |
Kim Nasmyth | 142 | 294 | 59231 |
Kenneth M. Yamada | 139 | 446 | 72136 |
Harold E. Varmus | 137 | 496 | 76320 |