While amphiphysin 2 uses its BAR domain to anchor to cell membranes and cause them to bend, it also has an SH3 domain at the other end that enables it to interact with other proteins, in particular dynamin 2, cavin 4 or another amphiphysin 2 molecule.
- Using a new approach to studying the interactome, the team at the IGBMC in Strasbourg discovered that the SH3 domain of amphiphysin 2 has many more protein partners, some of which are involved in neuromuscular diseases.
- By analysing the partners identified that interact with amphiphysin 2 through well-defined proline-rich motifs, the researchers found that many of them are involved in cell division.
- Thus, mutations in BIN1 that lead to a defect in the SH3 domain of amphiphysin 2 have consequences well beyond interactions with dynamin 2.
The authors conclude that this method of studying the interactome is not limited to identifying protein partners, but can also be used to assess the consequences of variants and validate their possible pathological nature.
