TY - JOUR
T1 - Interplay of Affinity and Surface Tethering in Protein Recognition
AU - Imran, Ali
AU - Moyer, Brandon S.
AU - Wolfe, Aaron J.
AU - Cosgrove, Michael S.
AU - Makarov, Dmitrii E.
AU - Movileanu, Liviu
N1 - Funding Information:
We thank our colleagues in the Movileanu and Cosgrove laboratories and at Ichor Life Sciences laboratories for their comments on the manuscript and stimulating discussions as well as for their technical assistance during the very early stage of this project. This work was supported by Robert A. Welch Foundation, Grant F-1514 (to D.E.M.), the National Science Foundation, Grant CHE 1955552 (to D.E.M.), the National Cancer Institute of the U.S. National Institutes of Health, Grant R01 CA140522 (to M.S.C.), and the National Institute of General Medical Sciences of the U.S. National Institutes of Health, Grant R01 GM129429 (to L.M.).
Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jpclett.2c00621
DO - 10.1021/acs.jpclett.2c00621
M3 - Article
C2 - 35485934
AN - SCOPUS:85130000612
SN - 1948-7185
SP - 4021
EP - 4028
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
ER -