Laboratory of Molecular Biology

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.

A hapten-specific chimaeric IgE antibody with human physiological effector function.

Abstract: Immunoglobulin E (IgE; see ref. 1) has a central role in allergic reactions although it rarely exceeds 5 µg ml−1 even in the serum of severely allergic individuals. Both mast cells and basophils possess receptors which bind the Fc portion of IgE with high affinity; crosslinking of membrane-bound IgE by allergen results in degranulation of the cell and release of a variety of pharmacologically active mediators including histamine. Myeloma IgE has been successfully used to block the skin sensitizing activity of allergic sera2; however, human myeloma IgE is clearly in limited supply. The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells3–5 has allowed us to construct a mouse cell line that secretes a chimaeric IgE, λ1 antibody whose heavy chain is composed of a human Ce constant region fused to a mouse variable (VH) region. This chimaeric IgE is specific for the hapten 4-hydroxy-3-nitro-phenacetyl (NP) and can, when crosslinked by antigen, trigger the degranulation of human basophils. When not crosslinked, however, the chimaeric IgE can prevent the passive sensitization of these cells by sera from allergic subjects.

Capturing the Structure of a Catalytic RNA Intermediate: The Hammerhead Ribozyme

Abstract: The crystal structure of an unmodified hammerhead RNA in the absence of divalent metal ions has been solved, and it was shown that this ribozyme can cleave itself in the crystal when divalent metal ions are added. This biologically active RNA fold is the same as that found previously for two modified hammerhead ribozymes. Addition of divalent cations at low pH makes it possible to capture the uncleaved RNA in metal-bound form. A conformational intermediate, having an additional Mg(II) bound to the cleavage-site phosphate, was captured by freeze-trapping the RNA at an active pH prior to cleavage. The most significant conformational changes were limited to the active site of the ribozyme, and the changed conformation requires only small additional movements to reach a proposed transition-state.