James M. McDonnell

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A variety of physiological death signals, as well as pathological cellular insults, trigger the genetically programmed pathway of apoptosis (Vaux and Korsmeyer 1999). Apoptosis manifests in two major execution programs downstream of the death signal: the caspase pathway and organelle dysfunction, of which mitochondrial dysfunction is the best characterized(More)
Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has(More)
The low-affinity immunoglobulin E (IgE) receptor, CD23 (FcepsilonRII), binds both IgE and CD21 and, through these interactions, regulates the synthesis of IgE, the antibody isotype that mediates the allergic response. We have determined the three-dimensional structure of the C-type lectin domain of CD23 in solution by nuclear magnetic resonance(More)
The role of IgE in allergic disease mechanisms is performed principally through its interactions with two receptors, FcεRI on mast cells and basophils, and CD23 (FcεRII) on B cells. The former mediates allergic hypersensitivity, the latter regulates IgE levels, and both receptors, also expressed on antigen-presenting cells, contribute to allergen uptake and(More)
MxiG is a single-pass membrane protein that oligomerizes within the inner membrane ring of the Shigella flexneri type III secretion system (T3SS). The MxiG N-terminal domain (MxiG-N) is the predominant cytoplasmic structure; however, its role in T3SS assembly and secretion is largely uncharacterized. We have determined the solution structure of MxiG-N(More)
CD46 is a complement regulator with important roles related to the immune response. CD46 functions as a pathogen receptor and is a potent costimulator for the induction of interferon-γ (IFN-γ)-secreting effector T helper type 1 (TH1) cells and their subsequent switch into interleukin 10 (IL-10)-producing regulatory T cells. Here we identified the Notch(More)
Among antibody classes, IgE has a uniquely slow dissociation rate from, and high affinity for, its cell surface receptor FcɛRI. We show the structural basis for these key determinants of the ability of IgE to mediate allergic hypersensitivity through the 3.4-Å-resolution crystal structure of human IgE-Fc (consisting of the Cɛ2, Cɛ3 and Cɛ4 domains) bound to(More)
p53 is a potent tumor suppressor with a crucial role in preventing uncontrolled cell proliferation and is therefore frequently deleted or mutated in cancer. For tumors with wild-type p53, its function can be overcome by overactive cellular antagonists, such as the ubiquitin ligase murine double minute clone 2 (MDM2). Restoring p53 activity by inhibiting(More)
A biologically active construct of the retroviral M domain from the avian Rous sarcoma virus is defined and its solution structure described. This M domain is fully active in budding and infectivity without myristylation. In spite of a sequence homology level that suggests no relationship among M domains and the family of matrix proteins in mammalian(More)
The interaction between IgE and its high affinity receptor (FcepsilonRI) is a critical step in the development of allergic responses. Detailed characterization of the IgE-FcepsilonRI interaction may offer insights into possible modes of inhibiting the interaction, which could thereby act as a potential therapy for allergy. In this study, NMR, CD, and(More)