Blog Posts

Now online at the journal Experimental Biology and Medicine: our new review article summarizing recent contributions from solid-state NMR and electron microscopy to further our understanding of the (mis)behavior of the mutant proteins behind Huntington’s disease.

Citation: 

I. Matlahov & P.C.A. van der Wel (2019) Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington’s disease. Exp. Biol. Med. in press; DOI: 10.1177/1535370219856620

Our first paper of 2019 has just appeared online in the journal Structure. It describes the very nice solid-state NMR studies performed by Dr. Mingyue Li, on a protein-lipid complex involved in the early stages of mitochondrial apoptosis. Together with our collaborators in the groups of Valerian Kagan and Jinwoo Ahn (University of Pittsburgh), she looked at the structure and function of the peroxidase active cytochrome c in its membrane-bound state. For more details on the findings, including how the lipid substrate cardiolipin forms membrane nano domains and acts as a dynamic regulator, please see the paper at the journal. This work was made possible by NIH funding (NIGMS R01 GM113908).

Reference:

Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics. Li, M., Mandal, A., Tyurin, V.A., Delucia, M., Ahn, J., Kagan, V.E., & Van der Wel, P.C.A. (2019) Structure,  in press [URL]

Additional information/press info:

EurekAlert

Congrats to Talia, Jennifer and Irina, as well as our international network of collaborators on the acceptance of an exciting new paper in JACS. It describes the power of dynamic nuclear polarization (DNP) to enable multidimensional solid-state NMR studies of polyglutamine-expanded huntingtin exon 1 fibrils. Importantly in these experiments we did not apply stable-isotope labeling to these protein deposits that are implicated in Huntington’s disease. This approach enables great structural data and can hopefully prove applicable to many more (types of) samples.

More info to follow, but for now: Read the accepted paper here at the journal.

Title: Structural fingerprinting of protein aggregates by DNP-enhanced solid-state NMR at natural isotopic abundance

Authors: Adam N. Smith, Katharina Märker, Talia Piretra, Jennifer C. Boatz, Irina Matlahov, Ravindra B. Kodali, Sabine Hediger, Patrick C.A. van der Wel, and Gaël De Paëpe

DOI: 10.1021/jacs.8b09002

Our new review article discussing the concept of dynamics-based spectral editing (DYSE) in ssNMR is now available online in the journal Methods. In it, we describe how the dynamics-sensitive pulse sequences enable the filtering out (or spectral editing) of signals based on their differences in dynamics. Applications by ourselves and many other groups are discussed. Notably, these applications range across a huge swatch of different sample types, going from designer peptide nano materials to whole tissues and even living organisms.

Citation:

• Hidden motions and motion-induced invisibility: dynamics-based spectral editing in solid-state NMR. Matlahov, I., Van der Wel, P.C.A. Methods, in press [URL]

Our new paper discussing the role of modern solid-state NMR in integrated structural biology is now published in Emerging Topics in Life Sciences. It provides a review of a selection of recent solid-state NMR studies from (mostly) the last decade. Not only does it give a review of notable 3D structures obtained by solid-state NMR, but it also examines contributions going beyond static protein structures. This includes the characterization of biologically relevant dynamics, and the pinpointing of crucial intermolecular interactions.

Reference:

• Patrick C.A. van der Wel (2018) “New applications of solid-state NMR in structural biology.” Emerging Topics in Life Sciences, Vol. 2, pp. 57–67

Access:

• DOI: 10.1042/ETLS20170088
• Request reprints by email: vanderwel@pitt.edu.
• Open Access PDF for download: OA PDF