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
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TL;DR: It is suggested that MSH2 (or factors dependent upon it) plays a role in the mechanism of mutation fixation is indicated by a strikingly increased focusing of the mutations on intrinsic hot spots, and two phases to hypermutation targeting are proposed.
366 citations
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TL;DR: The most potent immunotoxins are made from bacterial and plant toxins as discussed by the authors, which are composed of an antibody fragment linked to a toxin, and the immunotoxin binds to a surface antigen on a cancer cell, enters the cell by endocytosis, and kills it.
Abstract: Immunotoxins are proteins used to treat cancer that are composed of an antibody fragment linked to a toxin. The immunotoxin binds to a surface antigen on a cancer cell, enters the cell by endocytosis, and kills it. The most potent immunotoxins are made from bacterial and plant toxins. Refinements over many years have produced recombinant immunotoxins; these therapeutic proteins are made using protein engineering. Individual immunotoxins are designed to treat specific cancers. To date, most success has been achieved treating hematologic tumors. Obstacles to successful treatment of solid tumors include poor penetration into tumor masses and the immune response to the toxin component of the immunotoxin, which limits the number of cycles that can be given. Strategies to overcome these limitations are being pursued.
366 citations
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TL;DR: A phosphotriesterase with a very fast kcat (over 105 s−1), 63 times higher than the already very efficient wild‐type enzyme is selected using a novel strategy based on linking genotype and phenotype by in vitro compartmentalization using water‐in‐oil emulsions.
Abstract: We describe the selection of a phosphotriesterase with a very fast k(cat) (over 10(5) s(-1)), 63 times higher than the already very efficient wild-type enzyme. The enzyme was selected from a library of 3.4 x 10(7) mutated phosphotriesterase genes using a novel strategy based on linking genotype and phenotype by in vitro compartmentalization (IVC) using water-in-oil emulsions. First, microbeads, each displaying a single gene and multiple copies of the encoded protein, are formed by compartmentalized in vitro translation. These microbeads can then be selected for catalysis or binding. To select for catalysis the microbeads are re-emulsified in a reaction buffer of choice with a soluble substrate. The product and any unreacted substrate are coupled to the beads when the reaction is finished. Product-coated beads, displaying active enzymes and the genes that encode them, are detected with anti-product antibodies and selected using flow cytometry. This completely in vitro process selects for all enzymatic features simultaneously (substrate recognition, product formation, rate acceleration and turnover) and single enzyme molecules can be detected.
365 citations
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TL;DR: This work focuses on the many types of interactions that exist between the cytoskeleton and the plasma membrane, and discusses how membrane-cytoskeleton interactions are mediated and modulated, and how many proteins involved in these interactions are disrupted in human disease.
Abstract: Elements of the cytoskeleton interact intimately and communicate bidirectionally with cellular membranes. Such interactions are critical for a host of cellular processes. Here we focus on the many types of interactions that exist between the cytoskeleton and the plasma membrane to illustrate why these cellular components can never truly be studied in isolation in vivo. We discuss how membranecytoskeleton interactions are mediated and modulated, and how many proteins involved in these interactions are disrupted in human disease. We then highlight key molecular and physical variables that must be considered in order to mechanistically dissect events associated with changes in plasma membrane morphology. These considerations are integrated into the context of cell migration, filopodia formation, and clathrin-mediated endocytosis to show how a holistic view of the plasma membrane-cytoskeleton interface can allow for the appropriate interpretation of experimental findings and provide novel mechanistic insight into these important cellular events.
365 citations
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TL;DR: By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site‐directed mutagenesis, profiles are derived and used to classify C1 domains.
Abstract: C1 domains are compact alpha/beta structural units of about 50 amino acids which tightly bind two zinc ions. These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain 2 C1 domains (C1A and C1B) in their N-terminal regulatory regions. We present a comprehensive list of 54 C1 domains occurring singly or doubly in 34 different proteins. Many C1 domains and C1 domain-containing proteins bind phorbol esters, but many others do not. By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site-directed mutagenesis, profiles are derived and used to classify C1 domains. Twenty-six C1 domains fit the profile for phorbol-ester binding and are termed "typical." Twenty-eight other domains fit the profile for the overall C1 domain fold but do not fit the profile for phorbol ester binding, and are termed "atypical." Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not.
365 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 |