Latest about COVID-19 and W&M's Path Forward.

Info for... William & Mary
William & Mary W&M menu close William & Mary

New Publication: Journal of Physical Chemistry Letters 2021

Biophysical Chemistry, NMR Structural Biology, and Molecular Bioengineering Lab
Prof. Myriam Cotten
toc_0425_2021_for-wm-website.jpg
The Cotten lab has published an article in the Journal of Physical Chemistry (JPC) Letters, titled “Coordination of Redox Ions within a Membrane-Binding Peptide: A Tale of Aromatic Rings.” This excellent journal publishes short reports featuring “significant scientific advance and/or physical insight”. In the case of the Cotten lab, the study employs solid-state nuclear magnetic resonance and quantum calculations to identify stabilizing molecular interactions important to the anti-infective function of host defense peptides. Graduate student Mary Rooney contributed to this work. This research has relevance to a broad range of peptides and provide principles that could be used for applications in areas such as drug-resistance pathogens, neurological diseases, and biomedical imaging.”
figure1_atcun-optimized_extended-atcun_c_for-wm-website.jpg
Abstract:
The amino-terminal-copper-and-nickel-binding (ATCUN) motif, a tripeptide sequence ending with a histidine, confers important functions to proteins and peptides. Few high-resolution studies have been performed on the ATCUN motifs of membrane-associated proteins and peptides, limiting our understanding of how they stabilize Cu2+/Ni2+ in membranes. Here, we leverage solid-state NMR to investigate metal-binding to piscidin-1 (P1), a host-defense peptide featuring F1F2H3 as its ATCUN motif. Bound to redox ions, P1 chemically and physically damages pathogenic cell membranes. We design 13C/15N correlation experiments to detect and assign the deprotonated nitrogens produced and/or shifted by Ni2+-binding. Occupying multiple chemical states in P1-apo, H3 and the neighboring H4 respond to metalation by populating only the τ-tautomer. H3, as a proximal histidine, directly coordinates the metal, compared to the distal H4. Density functional theory calculations reflect this noncanonical arrangement and point toward cation−π interactions between the F1/F2/H4 aromatic rings and metal. These structural findings, which are relevant to other ATCUN-containing membrane peptides, could help design new therapeutics and materials for use in the areas of drug-resistant bacteria, neurological disorders, and biomedical imaging.
Citation:
Riqiang Fu*, Mary T. Rooney, Rongfu Zhang, and Myriam L. Cotten*
Cite this: J. Phys. Chem. Lett. 2021, 12, XXX, 4392–4399
Publication Date: May 3, 2021