Specific Interaction Sites Determine Differential Adsorption of Protein Structural Isomers on Nanoparticle Surfaces

Abstract

In biological systems, nanoparticles (NPs) elicit bioactivity upon interaction with proteins. As a result of post-translational modification, proteins occur in a variety of alternative covalent forms, including structural isomers, which present unique molecular surfaces. We aimed at a detailed description of the recognition of protein isomeric species by NP surfaces. The transient adsorption of isomeric ubiquitin (Ub) dimers by NPs was investigated by solution NMR spectroscopy. Lys63- and Lys48-linked Ub were adsorbed by large anionic NPs with different affinities, whereas the binding strength was similar in the cases of smaller particles. After the incorporation of paramagnetic tags into NPs, the observed site-resolved paramagnetic footprints provided a high-resolution map of the different protein surfaces binding to NPs. The approach described could be extended to further protein isoforms and more specialized NP systems to allow better control of the interactions between NPs and protein targets.

Semisynthetic Modification of Tau Protein with Di-Ubiquitin Chains for Aggregation Studies

“…Di-ubiquitin chains (Ub 2 ) were obtained from Ub variants through enzymatic reactions, with the strategy described in [ 46 , 47 ]. The reaction buffer contained 50 mM Tris HCl pH 8.0, 5 mM MgCl 2 , 10 mM ATP, 3 mM TCEP, 0.02% NaN 3 and protease inhibitors.…”

Luminescent Gold Nanorods To Enhance the Near‐Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach

“…The emission yield of these materials can be enhanced for potential applications in imaging, sensing, diagnosis, and therapy, but remains to be explored to its full extent . However, other nanostructures have been widely used for these applications, either due to their unique properties or due to their chemically controlled architectonics . GNRs can efficiently convert absorbed light into heat either through electron–electron interactions or electron–phonon interactions and have been established for their photothermal therapy (PTT) efficacy .…”

“…[5][6][7][8][9] However, other nanostructures have been widely used for these applications, either due to their uniquep roperties or due to their chemically controlled architectonics. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] GNRs can efficiently convert absorbed light into heat either through electron-electron interactions or electron-phonon interactions and have been established for their photothermal therapy (PTT) efficacy. [30,31] Furthermore, by incorporating ap hotosensitizer (PS) molecule, with ah igh singleto xygen yield, additional treatment modality,s uch as photodynamic therapy (PDT) could also be enabled in the same system, in addition to PTT.…”

Biomolecular interactions of ultrasmall metallic nanoparticles and nanoclusters

“…64 Nuclear magnetic resonance (NMR) is another powerful technique with the potential to unveil high resolution, residue-specic information on protein binding domains. [172][173][174][175][176][177][178] For example, NMR-based chemical shi perturbation was employed to identify the preferred binding poses of ubiquitin onto usGNPs surfacecoated with multimodal anionic ligands. 179 Mass spectrometry-based proteolysis studies have been also carried out to elucidate the preferred binding orientations of proteins adsorbed onto large NPs; [180][181][182][183][184] however, similar studies have yet to be implemented in the characterization of usGNP-protein complexes.…”