title: Deciphering the stepwise binding mode of HRG1β to HER3 by surface plasmon resonance and interaction map.
abstract: For the development of efficient anti-cancer therapeutics against the HER receptor family it is indispensable to understand the mechanistic model of the HER receptor activation upon ligand binding. Due to its high complexity the binding mode of Heregulin 1 beta (HRG1β) with its receptor HER3 is so far not understood. Analysis of the interaction of HRG1β with surface immobilized HER3 extracellular domain by time-resolved Surface Plasmon Resonance (SPR) was so far not interpretable using any regular analysis method as the interaction was highly complex. Here, we show that Interaction Map (IM) made it possible to shed light on this interaction. IM allowed deciphering the rate limiting kinetic contributions from complex SPR sensorgrams and thereby enabling the extraction of discrete kinetic rate components from the apparently heterogeneous interactions. We could resolve details from the complex avidity-driven binding mode of HRG1β with HER3 by using a combination of SPR and IM data. Our findings contribute to the general understanding that a major conformational change of HER3 during its activation is induced by a complex sequential HRG1β docking mode.
authors: Roche Diagnostics GmbH, Penzberg, Germany.
authors: Carmen
authors: C
authors: Peess
authors: Roche Diagnostics GmbH, Penzberg, Germany.
authors: Leopold
authors: L
authors: von Proff
authors: Roche Diagnostics GmbH, Penzberg, Germany.
authors: Sabine
authors: S
authors: Goller
authors: Ridgeview Diagnostics AB, Uppsala, Sweden.
authors: Karl
authors: K
authors: Andersson
authors: Roche Diagnostics GmbH, Penzberg, Germany.
authors: Michael
authors: M
authors: Gerg
authors: Ridgeview Diagnostics AB, Uppsala, Sweden.
authors: Magnus
authors: M
authors: Malmqvist
authors: Roche Innovation Center, Penzberg, Germany.
authors: Birgit
authors: B
authors: Bossenmaier
authors: Roche Diagnostics GmbH, Penzberg, Germany.
authors: Michael
authors: M
authors: Schräml
mesh_terms: D006801:Humans; D007700:Kinetics; D009369:Neoplasms / Q000188:drug therapy*; D020890:Neuregulin-1 / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D020890:Neuregulin-1; C087230:heregulin beta1; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3