TY - JOUR TI - The membrane-associated proteins FCHo and SGIP are allosteric activators of the AP2 clathrin adaptor complex AU - Hollopeter, Gunther AU - Lange, Jeffrey J AU - Zhang, Ying AU - Vu, Thien N AU - Gu, Mingyu AU - Ailion, Michael AU - Lambie, Eric J AU - Slaughter, Brian D AU - Unruh, Jay R AU - Florens, Laurence AU - Jorgensen, Erik M A2 - Pfeffer, Suzanne R VL - 3 PY - 2014 DA - 2014/10/10 SP - e03648 C1 - eLife 2014;3:e03648 DO - 10.7554/eLife.03648 UR - https://doi.org/10.7554/eLife.03648 AB - The AP2 clathrin adaptor complex links protein cargo to the endocytic machinery but it is unclear how AP2 is activated on the plasma membrane. Here we demonstrate that the membrane-associated proteins FCHo and SGIP1 convert AP2 into an open, active conformation. We screened for Caenorhabditis elegans mutants that phenocopy the loss of AP2 subunits and found that AP2 remains inactive in fcho-1 mutants. A subsequent screen for bypass suppressors of fcho-1 nulls identified 71 compensatory mutations in all four AP2 subunits. Using a protease-sensitivity assay we show that these mutations restore the open conformation in vivo. The domain of FCHo that induces this rearrangement is not the F-BAR domain or the ยต-homology domain, but rather is an uncharacterized 90 amino acid motif, found in both FCHo and SGIP proteins, that directly binds AP2. Thus, these proteins stabilize nascent endocytic pits by exposing membrane and cargo binding sites on AP2. KW - endocytosis KW - clathrin adaptor complex KW - AP2 KW - protein conformation KW - FCHo protein KW - SGIP1 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -