Unique structural features of a BCL-2 family protein CED-9 and biophysical characterization of CED-9/EGL-1 interactions

Jae Sung Woo, J. S. Jung, N. C. Ha, J. Shin, K. H. Kim, W. Lee, B. H. Oh

Research output: Contribution to journalArticle

32 Citations (Scopus)

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°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 1 H- 15 N 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.

Original languageEnglish
Pages (from-to)1310-1319
Number of pages10
JournalCell Death and Differentiation
Volume10
Issue number12
DOIs
Publication statusPublished - 2003 Dec 1
Externally publishedYes

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B-Cell Lymphoma
Temperature
Freezing
Membrane Proteins
Proteins
Bax protein (53-86)

Keywords

  • Apoptosis
  • BCL-2 family
  • CED-9
  • EGL-1
  • Molecular recognition

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Unique structural features of a BCL-2 family protein CED-9 and biophysical characterization of CED-9/EGL-1 interactions. / Woo, Jae Sung; Jung, J. S.; Ha, N. C.; Shin, J.; Kim, K. H.; Lee, W.; Oh, B. H.

In: Cell Death and Differentiation, Vol. 10, No. 12, 01.12.2003, p. 1310-1319.

Research output: Contribution to journalArticle

Woo, Jae Sung ; Jung, J. S. ; Ha, N. C. ; Shin, J. ; Kim, K. H. ; Lee, W. ; Oh, B. H. / Unique structural features of a BCL-2 family protein CED-9 and biophysical characterization of CED-9/EGL-1 interactions. In: Cell Death and Differentiation. 2003 ; Vol. 10, No. 12. pp. 1310-1319.
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