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1: J Mol Biol. 2006 Feb 17;356(2):367-81. Epub 2005 Dec 1.
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BCL-XL dimerization by three-dimensional domain swapping.

O'Neill JW, Manion MK, Maguire B, Hockenbery DM.

Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Dimeric interactions among anti- and pro-apoptotic members of the BCL-2 protein family are dynamically regulated and intimately involved in survival and death functions. We report the structure of a BCL-X(L) homodimers a 3D-domain swapped dimer (3DDS). The X-ray crystal structure demonstrates the mutual exchange of carboxy-terminal regions including BH2 (Bcl-2 homology 2) between monomer subunits, with the hinge region occurring at the hairpin turn between the fifth and sixth alpha helices. Both BH3 peptide-binding hydrophobic grooves are unoccupied in the 3DDS dimer and available for BH3 peptide binding, as confirmed by sedimentation velocity analysis. BCL-X(L) 3DDS dimers have increased pore-forming activity compared to monomers, suggesting that 3DDS dimers may act as intermediates in membrane pore formation. Chemical crosslinking studies of Cys-substituted BCL-X(L) proteins demonstrate that 3DDS dimers form in synthetic lipid vesicles.

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PMID: 16368107 [PubMed - indexed for MEDLINE]