Michael H. B. Stowell

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The nicotinic acetylcholine (ACh) receptor is the neurotransmitter-gated ion channel responsible for the rapid propagation of electrical signals between cells at the nerve/muscle synapse. We report here the 4.6 A structure of this channel in the closed conformation, determined by electron microscopy of tubular crystals of Torpedo postsynaptic membranes(More)
We have purified the mammalian synaptophysin/synaptobrevin (SYP/VAMP2) complex to homogeneity in the presence of cholesterol and determined the 3D EM structure by single particle reconstruction. The structure reveals that SYP and VAMP2 assemble into a hexameric ring wherein 6 SYP molecules bind 6 VAMP2 dimers. Using the EM map as a constraint, a three(More)
Intracellular vesicle fusion is mediated by SNAREs and Sec1/Munc18 (SM) proteins. Despite intensive efforts, the SNARE-SM mediated vesicle fusion reaction has not been faithfully reconstituted in biochemical assays. Here, we present an unexpected discovery that macromolecular crowding is required for reconstituting the vesicle fusion reaction in vitro.(More)
Synaptophysin I (SypI) is an archetypal member of the MARVEL-domain family of integral membrane proteins and one of the first synaptic vesicle proteins to be identified and cloned. Most all MARVEL-domain proteins are involved in membrane apposition and vesicle-trafficking events, but their precise role in these processes is unclear. We have purified(More)
Fusion of synaptic vesicles with the plasma membrane is mediated by the SNARE (soluble NSF attachment receptor) proteins and is regulated by synaptotagmin (syt). There are at least 17 syt isoforms that have the potential to act as modulators of membrane fusion events. Synaptotagmin IV (syt IV) is particularly interesting; it is an immediate early gene that(More)
We describe the design and production of a tobacco mosiac virus mutant that provides for specific and stoichiometric attachment of a wide variety of ligand-linker groups. As a result, specific ligands could be chemoselectively linked to the virion to produce highly diverse nanomolecular materials. These included semi-crystalline protein arrays and metallic(More)
Approximately 30% of the human genome, and likewise for other genomes, encodes membrane proteins. Also, the majority of known human pharmaceutical targets are membrane proteins. As a consequence, the future success of structure-based drug-design efforts will rely heavily on membrane-protein structural information. While a number of techniques are available(More)
Autoantibodies directed against the skeletal muscle acetylcholine receptor (AChR) play a critical role in the pathogenesis of the autoimmune disease, myasthenia gravis (MG). The pathogenic importance of anti-AChR antibodies is substantiated clinically by the often dramatic clinical improvement that follows removal of circulating antibodies utilizing(More)
Recently, the allosteric behavior of ion channels has been investigated by recording the individual steps leading to the complete activation of a cyclic nucleotide-gated ion channel. This information, in combination with recent studies on nicotinic acetylcholine receptor mutants, necessitates a modification of our current theories of the allosteric(More)