Institute for Protein Research, Osaka University^* Department of Molecular Biology, Osaka Bioscience Institute, Japan^** Department of Neurosurgery, School of Medicine, Oita University, Japan^*** Laboratory of Structural Proteomics, Institute for Protein Research, Osaka University, Japan^**** Department of Molecular Oncology, Osaka Bioscience Institute, Japan^***** Kyowa Hakko BioFrontier Laboratories, Japan^****** Research Institute for Microbial Diseases, Osaka University, Japan^******* Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Japan^********
○Harumi Hosaka^* Shigeru Hashimoto^** Mayumi Hirose^* Ari Hashimoto^** Masaki Morishige^*** Atsuko Yamada^** Ken-ichi Akagi^**** Eiji Ogawa^** Chitose Oneyama^***** Tsutomu Agatsuma^****** Masato Okada^******* Hidenori Kobayashi^*** Hiromi Wada^******** Hirofumi Nakano^****** Takahisa Ikegami^**** Atsushi Nakagawa^* Hisataka Sabe^**

We have shown that AMAP1 forms ternary complex with cortactin via its proline-rich region, and the complex are detected in invadopodia of highly invasive cancer cells. Since inhibition of the complex formation by a small chemical compound, UCS15A, effectively suppresses the cancer cell invasion, the ternary complex is possible therapeutic target for cancer treatment. We determined the structures of AMAP1/cortactin complex in solution by NMR spectroscopy and in crystal by X-ray crystallography. The SH3 domains generally bind to peptides with a one-to-one stoichiometry. However, we found that a single molecule of proline-rich peptide binds to two molecules of the cortactin SH3 domain in the crystal, in which the two SH3 domains were related to each other by non-crystallographic 2-fold symmetry. Furthermore, a small chemical compound, UCS15A, affected the region containing six proline residues of AMAP1.