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, Transcription (biology)
Papers published on a yearly basis
Papers
More filters
••
TL;DR: The effects of ROS on signal transduction pathways, the molecules that regulate intracellular ROS production and the potential protein targets of oxidants are focused on.
560 citations
••
TL;DR: A large body of data on the effect of antibiotics and mutations on translational fidelity is explained, such as the mechanism of activation of GTP hydrolysis by EF-Tu, and the relationship between decoding and frameshifting.
Abstract: ▪ Abstract The underlying basis for the accuracy of protein synthesis has been the subject of over four decades of investigation. Recent biochemical and structural data make it possible to understand at least in outline the structural basis for tRNA selection, in which codon recognition by cognate tRNA results in the hydrolysis of GTP by EF-Tu over 75 A away. The ribosome recognizes the geometry of codon-anticodon base pairing at the first two positions but monitors the third, or wobble position, less stringently. Part of the additional binding energy of cognate tRNA is used to induce conformational changes in the ribosome that stabilize a transition state for GTP hydrolysis by EF-Tu and subsequently result in accelerated accommodation of tRNA into the peptidyl transferase center. The transition state for GTP hydrolysis is characterized, among other things, by a distorted tRNA. This picture explains a large body of data on the effect of antibiotics and mutations on translational fidelity. However, many fu...
559 citations
••
TL;DR: A general model for what can be thought of as a triage system for handling misfolded proteins in vivo is proposed, assuring swift re folding of proteins with functional potential and rapid degradation of irreversibly denatured or damaged pro teins.
Abstract: Proteases and chaperones together serve to maintain quahty control of cellular proteins. Both types of en zymes have as their substrates the variety of misfolded and partially folded proteins that arise from slow rates of folding or assembly, chemical or thermal stress, intrinsic structural instability, and biosynthetic errors. The pri mary function of classical chaperones, such as the Esch erichia coh DnaK/Hsp70 and its cochaperones, DnaJ and GrpE, and GroEL/Hsp60 and its cochaperone, GroES, is to modulate protein folding pathways, thereby prevent ing misfolding and aggregation, promoting refolding and proper assembly. Recent work has demonstrated that ATP-dependent proteases, as well as closely related pro teins, have intrinsic chaperone activity, suggesting that the initial steps in energy-dependent protein degradation may be similar to those of chaperone-dependent protein folding. The classical chaperones are also required for degradation of certain proteins in vivo, but we propose below that generally they affect proteolysis indirectly by maintaining proteins in soluble forms that would other wise aggregate and become inaccessible to proteases. In this review we present the evidence linking the activi ties of chaperones and proteases, and propose a general model for what can be thought of as a triage system for handling misfolded proteins in vivo, assuring swift re folding of proteins with functional potential and rapid degradation of irreversibly denatured or damaged pro teins.
558 citations
••
TL;DR: It is demonstrated that CNS precursor cell populations expanded in vitro can efficiently differentiate into dopaminergic neurons, survive intrastriatal transplantation and induce functional recovery in hemiparkinsonian rats.
Abstract: In vitro expansion of central nervous system (CNS) precursors might overcome the limited availability of dopaminergic neurons in transplantation for Parkinson's disease, but generating dopaminergic neurons from in vitro dividing precursors has proven difficult. Here a three-dimensional cell differentiation system was used to convert precursor cells derived from E12 rat ventral mesencephalon into dopaminergic neurons. We demonstrate that CNS precursor cell populations expanded in vitro can efficiently differentiate into dopaminergic neurons, survive intrastriatal transplantation and induce functional recovery in hemiparkinsonian rats. The numerical expansion of primary CNS precursor cells is a new approach that could improve both the ethical and the technical outlook for the use of human fetal tissue in clinical transplantation.
557 citations
••
TL;DR: It is proposed that flotillin-1 is one determinant of a clathrin-independent endocytic pathway in mammalian cells and resides in punctate structures within the plasma membrane and in a specific population of endocytosis intermediates.
Abstract: Previous studies provide evidence for an endocytic mechanism in mammalian cells that is distinct from both clathrin-coated pits and caveolae1,2,3,4,5, and is not inhibited by overexpression of GTPase-null dynamin mutants1,2,3,4,6. This mechanism, however, has been defined largely in these negative terms. We applied a ferro-fluid-based purification of endosomes to identify endosomal proteins. One of the proteins identified in this way was flotillin-1 (also called reggie-2)7,8. Here, we show that flotillin-1 resides in punctate structures within the plasma membrane and in a specific population of endocytic intermediates. These intermediates accumulate both glycosylphosphatidylinositol (GPI)-linked proteins and cholera toxin B subunit4,9. Endocytosis in flotillin-1-containing intermediates is clathrin-independent. Total internal reflection microscopy and immuno-electron microscopy revealed that flotillin-1-containing regions of the plasma membrane seem to bud into the cell, and are distinct from clathrin-coated pits and caveolin-1-positive caveolae10. Flotillin-1 small interfering RNA (siRNA) inhibited both clathrin-independent uptake of cholera toxin and endocytosis of a GPI-linked protein. We propose that flotillin-1 is one determinant of a clathrin-independent endocytic pathway in mammalian cells.
556 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 |