Tag: cardiolipin

Publication: Protocols for membrane protein studies by solid-state NMR (including drug interactions)
Standard / by / March 26, 2025 / No Comments

Our invited ‘protocol’ paper is now available in the journal Protein Science (Protein Society), authored by Alessia Lasorsa and Patrick van der Wel. In this report we described our “Solid-state NMR protocols for unveiling dynamics and (drug) interactions of membrane-bound proteins”. This paper was based on an invitation to contribute to the “Tools for Protein Science 2025” special issue. We opted for contributing a discussion of how we use solid-state NMR to probe membrane-bound proteins. More specifically, we summarized protocols we developed in years of work on mitochondrial lipid-protein interactions. A special focus in the report is on some recent work with the group of Valerian Kagan (at journal) where we probed how drug-like compounds can bind a pathogenic protein-lipid complex relevant to Barth Syndrome. We hope that the resulting manuscript is a useful reference work for people working on these topics, and in particular also for introducing new ssNMR users to relevant procedures (and their rationales). 

We acknowledge the funding support of the Barth Syndrome Foundation, who is currently supporting the related work in the lab.

Reference:

Lasorsa, A., Van der Wel, P.C.A. (2025) Solid-state NMR protocols for unveiling dynamics and (drug) interactions of membrane-bound proteins. Protein Science 34: e70102. [DOI]

Publication: Structural and motional changes in a cytochrome c – lipid complex implicated in apoptosis.
Standard / by / July 20, 2021 / No Comments

Congratulations to lab alum Dr. Mingyue Li and our collaborators on the publication of a new paper in the Journal of Molecular Biology. The paper is online via its DOI link. The paper describes how we used solid-state NMR spectroscopy to characterise the partial destabilization of the native fold of the protein cytochrome c, as it is bound to cardiolipin lipids. This protein-lipid complex is implicated in the process of programmed cell death, where it plays a key role in triggering the self-destruction of undesired or disease cells in higher organisms. Notably, the CL-bound protein catalyses the process of mitochondrial lipid peroxidation, which we see being reconstituted in vitro via mass-spectrometry lipidomics. The latter work is done by our longstanding collaborators in the group of Valerian Kagan at the University of Pittsburgh. The current paper builds on our earlier work, but is of especial interest based on the fact that we bridge some of our prior findings (that suggested the protein to be surprisingly “folded” on the membrane) to studies that report a greater degree of mobility of the CL-bound protein. Here we see how the experimental conditions regulate protein mobility and also pinpoint how different extents of mobility are present in the membrane-bound cytochrome c. Interestingly, the regional dynamics map partly, but not completely onto the previously identified “foldons” that define the folding landscape of this widely studied mitochondrial protein. For more details see the paper below. It is available as #openaccess so just follow the DOI link for access:


Reference:
Mingyue Li, Wanyang Sun, Vladimir A. Tyurin, Maria DeLucia, Jinwoo Ahn, Valerian E. Kagan, Patrick C.A. van der Wel (2021) Activation of Cytochrome C Peroxidase Function Through Coordinated Foldon Loop Dynamics upon Interaction with Anionic Lipids, Journal of Molecular Biology, Volume 433, Issue 15, 23 July 2021, 167057