Megalin - gentamicin interaction

The antibiotic gentamicin is used to treat severe infections. If it is administered in high doses it can be nephrotoxic, because it enters kidney cells by binding to the receptor megalin.

To understand its interaction with megalin, NMR titration data can be used to create a 3D model of the megalin-gentamicin complex. This is achieved by investigating the changes in chemical shifts in megalin when an excess of gentamicin is added. In this case, megalin is saturated with gentamicin and all signals originate from the megalin-gentamicin complex. When compared to the signals from the reference sample with megalin alone, the amino acids involved in the interaction can be determined.

Figure 1: Megalin-gentamicin interaction