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Our new review article summarizing recent findings on protein aggregation enabled by solid-state NMR is now online. This “Trends” article will appear in the journal Solid-state Nuclear Magnetic Resonance in Nov. 2017 (DOI 10.1016/j.ssnmr.2017.10.001). In the paper we examine and summarize some of the exciting new insights into the molecular mechanisms behind protein misfolding and aggregation that have been enabled by a range of recent ssNMR studies. This includes the various new amyloid structures deposited in the PDB, with links to these entries provided below: 5OQV 2M5N 2LNQ 2MVX 2MXU 5KK3 2NAO 2M4J 5W3N 2N1E 2N0A Reference: [1] Van der Wel, […]

Congratulations to lab alum Dr. Hsiang-Kai Lin, graduate student Jennifer Boatz, and our collaborators locally and abroad! Our new publication describing the structure and properties of mutant huntingtin exon 1 fibrils has been published in the journal Nature Communications. The paper describes our ongoing studies of the mutant protein behind the devastating neurodegeneration in Huntington’s Disease. Biochemical and structural experiments show that mutant huntingtin exon 1 forms at least two types of neurotoxic aggregates with different internal structures.  Through the use of solid-state NMR spectroscopy and electron microscopy we look at the molecular details of these structural differences. Various other disease-related amyloid proteins have a similar tendency […]

Congratulations to Jennifer Boatz, Dr. Mingyue Li and our collaborators in the Gronenborn lab for the publication of our new paper on cataract-related protein aggregation. Our newly published report in Nature Communications looks at the structure of a mutant protein (P23T γD crystallin) associated with inherited cataract disease, when it is aggregated. Interestingly, the same protein forms very different kinds of deposits depending on the conditions under which it aggregates: a common type of aggregate “polymorphism”. In many studies of protein aggregation, the protein of interest is made to form aggregates by exposure to acidic conditions. This cataract protein also aggregates well under such […]

Congratulations to Abhishek and Jennifer on having our new paper accepted for publication in the Journal of Biomolecular NMR. In it Abhishek describes the use of custom-built ultracentrifuge sample packing devices for the preparation of solid-state NMR samples. Publication info: On the use of ultracentrifugal devices for routine sample preparation in biomolecular magic-angle-spinning NMR. Mandal, A., Boatz, J.C., Wheeler, T., and Van der Wel, P.C.A. (2017) J. Biomol. NMR in press. DOI Access it via this sharing link: http://rdcu.be/px5r  

In a new report in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) we provide important new insights into the misfolding and aggregation behavior of the mutant protein that causes Huntington’s Disease (HD). First authors Dr Cody Hoop and Dr Hsiang-Kai (Kyle) Lin used advanced solid-state NMR spectroscopy to study the structure of fibrils formed by huntingtin exon1 and related polyglutamine proteins. These state-of-the-art experiments allow us to elucidate a new beta-hairpin-based structure for the polyglutamine fibril core. In addition, our results provide important new insights into the stochastic self-assembly mechanism of expanded polyglutamine. This […]

Congratulations to Abhishek and his co-authors! The Biophysical Journal has accepted our paper on the structural and functional study of cardiolipin-bound cytochrome c, looking at its peroxidase activated membrane-bound state. Lipid oxidation by cytochrome c plays a critical role in mitochondrial apoptosis, and we examined the molecular underpinnings of this process using solid-state NMR spectroscopy and other tools. For more information see the paper: Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., Van der Wel, P.C.A.* (2015) Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Biophys. J. J. 109(9): 1873–1884 (Full text)

New publication on the structure and dynamics in fibrils formed from mutant huntingtin fragments, including a 44-Q exon-1. In the journal Biochemistry: Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state NMR. DOI:http://dx.doi.org/10.1021/bi501010q

New publication on the surprising features of D-polyQ, in the Journal of Molecular Biology: D-polyglutamine amyloid recruits L-polyglutamine monomers and kills cells. DOI:http://dx.doi.org/10.1016/j.jmb.2013.11.019

Jun Li’s work on rotational resonance width experiments is published in JMR: Li, J., & van der Wel, P.C.A. Spinning-rate encoded chemical shift correlations from rotational resonance solid-state NMR experiments. Journal of Magnetic Resonance. 2013;230:117-124.  http://dx.doi.org/10.1016/j.jmr.2013.02.004

Cody’s collaborative work with the Wetzel group on the structure and formation mechanism of polyglutamine aggregates is published in JMB: Kar, K., Hoop, C.L., Drombosky, K.W., Baker, M.A., Kodali, R., Arduini, I., van der Wel, P.C.A., Horne, W.S., & Wetzel, R. β-hairpin-mediated nucleation of polyglutamine amyloid formation. J Mol Biol. 2013;425(7):1-45. See:  http://dx.doi.org/10.1016/j.jmb.2013.01.016