The surface accessibility of {\alpha}-bungarotoxin monitored by a novel paramagnetic probe

TL;DR

This study introduces a new paramagnetic probe, Gd2L7, to assess the surface accessibility of { extalpha}-bungarotoxin, revealing common approach pathways and the influence of protein flexibility and hydration on probe interaction.

Contribution

The paper presents a novel Gd2L7 probe and demonstrates its effectiveness in mapping { extalpha}-bungarotoxin surface accessibility, comparing it with existing probes and analyzing interaction pathways.

Findings

Gd2L7 and GdDTPA-BMA share similar approach pathways to the toxin surface.

Protein flexibility and hydration influence probe approach to the binding site.

Both probes preferentially target the toxin region involved in receptor interaction.

Abstract

The surface accessibility of {\alpha}-bungarotoxin has been investigated by using Gd2L7, a newly designed paramagnetic NMR probe. Signal attenuations induced by Gd2L7 on {\alpha}-bungarotoxin C{\alpha}H peaks of 1H-13C HSQC spectra have been analyzed and compared with the ones previously obtained in the presence of GdDTPA-BMA. In spite of the different molecular size and shape, for the two probes a common pathway of approach to the {\alpha}-bungarotoxin surface can be observed with an equally enhanced access of both GdDTPA-BMA and Gd2L7 towards the protein surface side where the binding site is located. Molecular dynamics simulations suggest that protein backbone flexibility and surface hydration contribute to the observed preferential approach of both gadolinium complexes specifically to the part of the {\alpha}-bungarotoxin surface which is involved in the interaction with its physiological target, the nicotinic acetylcholine receptor.