Involvement of the N-terminus of Bax in its intracellular localization and function

FEBS Lett. 2002 Feb 13;512(1-3):95-100. doi: 10.1016/s0014-5793(02)02227-5.

Abstract

We have identified, using site-directed mutagenesis, a proline located at position 13 of Baxalpha (Bax) as crucial for the maintenance of its cytosolic conformation. The substitution of this proline by a valine results in a strong binding of Bax to mitochondria and to conformational changes monitored by a decreased sensitivity of Bax to mild proteolysis and the enhancement of its oligomerization state. Deletion of the C-terminus of Bax does not modify its intracellular localization. On the other hand, the pro-apoptotic activity of Bax is enhanced by a deletion of the C-terminus in the absence of the N-terminus but is decreased in its presence. These results suggest that both extremities functionally interact to control the activity but not the subcellular localization of Bax.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / metabolism
  • Cell Compartmentation*
  • Cytosol / metabolism
  • Intracellular Membranes / metabolism
  • Mitochondria, Liver / metabolism
  • Molecular Sequence Data
  • Mutation
  • Proline / genetics
  • Proline / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2*
  • bcl-2-Associated X Protein

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Proline