Unique structural features of a BCL-2 family protein CED-9 and biophysical characterization of CED-9/EGL-1 interactions |
| |
Authors: | Woo J-S Jung J-S Ha N-C Shin J Kim K-H Lee W Oh B-H |
| |
Affiliation: | Department of Life Science, Center for Biomolecular Recognition and Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea. |
| |
Abstract: | The interactions between B-cell lymphoma 2 (BCL-2) family members are known to be mediated through the binding of the BH3 domain of a proapoptotic member to the BH3-binding groove of an antiapoptotic member. We determined the crystal structure of antiapoptotic CED-9, which reveals a unique C-terminal helix altering the common BH3-binding region. A coexpression system to produce CED-9 in complex with proapoptotic EGL-1 enabled us to show that the binding of EGL-1 to CED-9 is extremely stable, raising the melting temperature (T(M)) of CED-9 by 25 degrees C, and that the binding surface of CED-9 extends beyond the BH3-binding region and reaches the BH4 domain. Consistently, the T(M) and a 1H-15N correlation NMR spectrum of CED-9 in complex with EGL-1 are drastically different from those of CED-9 in complex with the EGL-1 BH3 peptide. The data suggest that the recognition between other BCL-2 family members may also involve much wider protein surfaces than is previously thought. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|