news
Publication: Molecular structure and misfolding mechanism of expanded polyglutamine proteins.
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 protein misfolding mechanism is likely active not only in HD, but also in other CAG repeat expansion disorders. The newfound molecular understanding of these disease-causing processes may facilitate the rational design of aggregation-modulating treatments or drugs.
For more information, read the article at PNAS.
Publication: Solid-state NMR studies of the pro-apoptotic peroxidase-form of cytochrome c.
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)
Publication – Hoop et al (2014) “Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state NMR.”
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
Publication – D-polyglutamine amyloid recruits L-polyglutamine monomers and kills cells.
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
Publication – Spinning-rate encoded chemical shift correlations from rotational resonance solid-state NMR experiments
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
Publication – β-hairpin-mediated nucleation of polyglutamine amyloid formation
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.