Interplay of Affinity and Surface Tethering in Protein Recognition.

Autor: Imran A; Department of Physics, Syracuse University, 201 Physics Building, Syracuse, New York 13244-1130, United States., Moyer BS; Ichor Life Sciences, Inc., 2651 US Route 11, LaFayette, New York 13084, United States.; Lewis School of Health Sciences, Clarkson University, 8 Clarkson Avenue, Potsdam, New York 13699, United States., Wolfe AJ; Department of Physics, Syracuse University, 201 Physics Building, Syracuse, New York 13244-1130, United States.; Ichor Life Sciences, Inc., 2651 US Route 11, LaFayette, New York 13084, United States.; Lewis School of Health Sciences, Clarkson University, 8 Clarkson Avenue, Potsdam, New York 13699, United States.; Department of Chemistry, State University of New York College of Environmental Science and Forestry, 1 Forestry Dr., Syracuse, New York 13210, United States., Cosgrove MS; Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, 4249 Weiskotten Hall, 766 Irving Avenue, Syracuse, New York 13210, United States., Makarov DE; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.; Oden Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas 78712, United States., Movileanu L; Department of Physics, Syracuse University, 201 Physics Building, Syracuse, New York 13244-1130, United States.; Department of Biomedical and Chemical Engineering, Syracuse University, 329 Link Hall, Syracuse, New York 13244, United States.; The BioInspired Institute, Syracuse University, Syracuse, New York 13244, United States.
Jazyk: angličtina
Zdroj: The journal of physical chemistry letters [J Phys Chem Lett] 2022 May 12; Vol. 13 (18), pp. 4021-4028. Date of Electronic Publication: 2022 Apr 29.
DOI: 10.1021/acs.jpclett.2c00621
Abstrakt: Surface-tethered ligand-receptor complexes are key components in biological signaling and adhesion. They also find increasing utility in single-molecule assays and biotechnological applications. Here, we study the real-time binding kinetics between various surface-immobilized peptide ligands and their unrestrained receptors. A long peptide tether increases the association of ligand-receptor complexes, experimentally proving the fly casting mechanism where the disorder accelerates protein recognition. On the other hand, a short peptide tether enhances the complex dissociation. Notably, the rate constants measured for the same receptor, but under different spatial constraints, are strongly correlated to one another. Furthermore, this correlation can be used to predict how surface tethering on a ligand-receptor complex alters its binding kinetics. Our results have immediate implications in the broad areas of biomolecular recognition, intrinsically disordered proteins, and biosensor technology.
Databáze: MEDLINE