title: Analysis of interaction sites in homo- and heteromeric complexes containing Bcl-2 family members and the cellular prion protein.
abstract: The cellular prion protein (PrP) binds to the C-terminus of Bcl-2 but not Bax. Therefore, we examined whether the C-terminus of Bcl-2 was important for other homomeric and heteromeric protein-protein interactions. Using the yeast two hybrid system and co-immunoprecipitation, three sites of homomeric interactions were identified within Bcl-2. The carboxy terminal 37 amino acids selectively homodimerized. Two additional regions of Bcl-2 (residues 1-129 and 126-200) interacted with each other, but not themselves permitting both intra- and intermolecular association. In addition, we analyzed heteromeric interactions of Bcl-2 with PrP and two Bcl-2 related proteins, Bax and A1. The domain requirements for binding of those three proteins to Bcl-2 were different from one another. Bax binding required almost the entire Bcl-2 molecule, while A1 bound to the amino terminal region (residues 1-82). PrP associated with the carboxy terminus of Bcl-2 (amino acids 200-236). These data suggest configurational models for Bcl-2 containing complexes. First, Bcl-2 may exist as both heterodimers and heteromultimers. Second, molecules such as Bax and A1 may serve to cap chains of Bcl-2 homodimers by interacting with dimerization domains in the extramembrane region. PrP may disrupt chains of Bcl-2 molecules at the homomeric association site in the transmembrane region.
authors: St. Jude Children's Research Hospital, Department of Developmental Neurobiology, Memphis, TN 38105, USA.
authors: C
authors: C
authors: Kurschner
authors: J I
authors: JI
authors: Morgan
mesh_terms: D006822:Hybrid Cells / Q000378:metabolism*; D011233:Precipitin Tests; D011328:Prions / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
chemical_list: D011328:Prions; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein