Michael T. Bowers

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In recent years, small protein oligomers have been implicated in the aetiology of a number of important amyloid diseases, such as type 2 diabetes, Parkinson's disease and Alzheimer's disease. As a consequence, research efforts are being directed away from traditional targets, such as amyloid plaques, and towards characterization of early oligomer states.(More)
A portion of the prion protein, PrP106-126, is highly conserved among various species and is thought to be one of the key domains involving amyloid formation of the protein. We used ion mobility spectrometry-mass spectrometry (IMS-MS) in conjunction with replica exchange molecular dynamics (REMD) to examine the monomeric and oligomeric structures of normal(More)
Recently, certain C-terminal fragments (CTFs) of Aβ42 have been shown to be effective inhibitors of Aβ42 toxicity. Here, we examine the interactions between the shortest CTF in the original series, Aβ(39-42), and full-length Aβ. Mass spectrometry results indicate that Aβ(39-42) binds directly to Aβ monomers and to the n = 2, 4, and 6 oligomers. The(More)
Abeta40 and Abeta42 are peptides that adopt similar random-coil structures in solution. Abeta42, however, is significantly more neurotoxic than Abeta40 and forms amyloid fibrils much more rapidly than Abeta40. Here, mass spectrometry and ion mobility spectrometry are used to investigate a mixture of Abeta40 and Abeta42. The mass spectrum for the mixed(More)
G-rich DNA sequences are able to fold into structures called G-quadruplexes. To obtain general trends in the influence of loop length on the structure and stability of G-quadruplex structures, we studied oligodeoxynucleotides with random bases in the loops. Sequences studied are dGGGW(i)GGGW(j)GGGW(k)GGG, with W = thymine or adenine with equal probability,(More)
Oligomerization of human islet amyloid polypeptide (IAPP) has been increasingly considered a pathogenic process in type II diabetes. Here structural features of the IAPP monomer have been probed using a combination of ion mobility mass spectrometry (IMS-MS) and all-atom replica exchange molecular dynamics (REMD) simulations. Three distinct conformational(More)
The combination of mass spectrometry and ion mobility spectrometry (IMS) employing a temperature-variable drift cell or a drift tube divided into sections to make IMS-IMS experiments possible allows information to be obtained about the molecular dynamics of polyatomic ions in the absence of a solvent. The experiments allow the investigation of structural(More)
Amyloid cascades that lead to peptide β-sheet fibrils and plaques are central to many important diseases. Recently, intermediate assemblies of these cascades were identified as the toxic agents that interact with cellular machinery. The location and cause of the transformation from a natively unstructured assembly to the β-sheet oligomers found in all(More)
The conformations of desolvated ubiquitin ions, lifted into the gas phase by electrospray ionization (ESI), were characterized by ion mobility spectrometry (IMS) and compared to the solution structures they originated from. The IMS instrument combining a two-meter helium drift tube with a quadrupole time-of-flight mass spectrometer was built in-house.(More)
The amyloid beta-protein (Abeta) is a seminal neuropathic agent in Alzheimer's disease (AD). Recent evidence points to soluble Abeta oligomers as the probable neurotoxic species. Among the naturally occurring Abeta peptides, the 42-residue form Abeta42 is linked particularly strongly with AD, even though it is produced at approximately 10% of the levels of(More)