@article {2018|2134,
	title = {DNA Binding Induces a Nanomechanical Switch in the RRM1 Domain of TDP-43},
	journal = {J Phys Chem Lett},
	volume = {9},
	year = {2018},
	month = {Jul},
	pages = {3800-3807},
	abstract = {<p>Understanding the molecular mechanisms governing protein-nucleic acid interactions is fundamental to many nuclear processes. However, how nucleic acid binding affects the conformation and dynamics of the substrate protein remains poorly understood. Here we use a combination of single molecule force spectroscopy AFM and biochemical assays to show that the binding of TG-rich ssDNA triggers a mechanical switch in the RRM1 domain of TDP-43, toggling between an entropic spring devoid of mechanical stability and a shock absorber bound-form that resists unfolding forces of \&sim;40 pN. The fraction of mechanically resistant proteins correlates with an increasing length of the TG n oligonucleotide, demonstrating that protein mechanical stability is a direct reporter of nucleic acid binding. Steered molecular dynamics simulations on related RNA oligonucleotides reveal that the increased mechanical stability fingerprinting the holo-form is likely to stem from a unique scenario whereby the nucleic acid acts as a \&quot;mechanical staple\&quot; that protects RRM1 from mechanical unfolding. Our approach highlights nucleic acid binding as an effective strategy to control protein nanomechanics.</p>
},
	doi = {10.1021/acs.jpclett.8b01494},
	author = {Wang, Yong Jian and Rico-Lastres, Palma and Lezamiz, Ainhoa and Mora, Marc and Solsona, Carles and Guillaume Stirnemann and Garcia-Manyes, Sergi}
}
@article {2015|1729,
	title = {The mechanochemistry of copper reports on the directionality of unfolding in model cupredoxin proteins.},
	journal = {Nature Comm.},
	volume = {6},
	year = {2015},
	pages = {7894},
	abstract = {<p>Understanding the directionality and sequence of protein unfolding is crucial to elucidate the underlying folding free energy landscape. An extra layer of complexity is added in metalloproteins, where a metal cofactor participates in the correct, functional fold of the protein. However, the precise mechanisms by which organometallic interactions are dynamically broken and reformed on (un)folding are largely unknown. Here we use single molecule force spectroscopy AFM combined with protein engineering and MD simulations to study the individual unfolding pathways of the blue-copper proteins azurin and plastocyanin. Using the nanomechanical properties of the native copper centre as a structurally embedded molecular reporter, we demonstrate that both proteins unfold via two independent, competing pathways. Our results provide experimental evidence of a novel kinetic partitioning scenario whereby the protein can stochastically unfold through two distinct main transition states placed at the N and C termini that dictate the direction in which unfolding occurs.</p>},
	isbn = {doi:10.1038/ncomms8894},
	issn = {2041-1723},
	doi = {10.1038/ncomms8894},
	url = {http://www.nature.com/ncomms/2015/150803/ncomms8894/abs/ncomms8894.html},
	author = {Beedle, Amy E M and Lezamiz, Ainhoa and Guillaume Stirnemann and Garcia-Manyes, Sergi}
}
