Figures & data
Figure 1. A proposed mechanism for the allosteric regulation of GRB2. Allosteric regulation of GRB2 is a multi-step process that appear to be a functional prerequisite for potential bivalent SOS1 binding. It possibly starts with the interaction of SOS1 proline-rich motif 3 (PRM 3) with GRB2 nSH3 domain (i). The cytosolic, heterodimeric, inactive GRB2-SOS1 complex translocates to dimerized, tyrosine-phosphorylated HER2 receptor, where pYP binding of the SH2 domain (ii) may induce its association with phospholipids of the plasma membrane (iii), as proposed by Park et al. [Citation57]. This event may not only increase the dwell time of GRB2-SOS1 complex at the membrane but rather triggers the release of cSH3 from its interaction with SH2 (iv) and the subsequent back-to-back interaction of cSH3 with nSH3 (v). This cooperative mechanism now allows cSH3 to bind SOS1 PRM 4 (vi) and ultimately induces among other events the SOS1-catalysed RAS activation (vii).
![Figure 1. A proposed mechanism for the allosteric regulation of GRB2. Allosteric regulation of GRB2 is a multi-step process that appear to be a functional prerequisite for potential bivalent SOS1 binding. It possibly starts with the interaction of SOS1 proline-rich motif 3 (PRM 3) with GRB2 nSH3 domain (i). The cytosolic, heterodimeric, inactive GRB2-SOS1 complex translocates to dimerized, tyrosine-phosphorylated HER2 receptor, where pYP binding of the SH2 domain (ii) may induce its association with phospholipids of the plasma membrane (iii), as proposed by Park et al. [Citation57]. This event may not only increase the dwell time of GRB2-SOS1 complex at the membrane but rather triggers the release of cSH3 from its interaction with SH2 (iv) and the subsequent back-to-back interaction of cSH3 with nSH3 (v). This cooperative mechanism now allows cSH3 to bind SOS1 PRM 4 (vi) and ultimately induces among other events the SOS1-catalysed RAS activation (vii).](/cms/asset/d34eebd3-e92f-4db2-bd0c-639f5b531561/ksgt_a_2089001_f0001_oc.jpg)