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)
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)
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)
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)
The thesis entitled: In vitro selections for imidazole-modified RNA catalysts written by Cara L. Florance has been approved for the Department of Chemistry and Biochemistry. Date The final copy of this thesis has been examined by the signatories, and we find that both the content and the form meet acceptable presentation standards of scholarly work in the(More)
We demonstrate that membrane proteins and phospholipids can self-assemble into polyhedral arrangements suitable for structural analysis. Using the Escherichia coli mechanosensitive channel of small conductance (MscS) as a model protein, we prepared membrane protein polyhedral nanoparticles (MPPNs) with uniform radii of ∼ 20 nm. Electron cryotomographic(More)