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Lookup NU author(s): Dr Helen WallerORCiD, Professor Jeremy LakeyORCiD
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Controlled cell death is fundamental to tissue hemostasis and apoptosis malfunctions can lead to a wide range of diseases. Bcl-xL is an anti-apoptotic protein the function of which is linked to its reversible interaction with mitochondrial outer membranes. Its interfacial and intermittent bilayer association makes prediction of its bound structure difficult without using methods able to extract data from dynamic systems. Here we investigate Bcl-xL associated with oriented lipid bilayers at physiological pH using solid-state NMR spectroscopy. The data are consistent with a C-terminal transmembrane anchoring sequence and an average alignment of the remaining helices, i.e. including helices 5 and 6, approximately parallel to the membrane surface. Data from several biophysical approaches confirm that after removal of the C-terminus from Bcl-xL its membrane interactions are weak. In the presence of membranes Bcl-xL can still interact with a Bak BH3 domain peptide suggesting a model where the hydrophobic C-terminus of the protein unfolds and inserts into the membrane. During this conformational change the Bcl-xL hydrophobic binding pocket becomes accessible for protein-protein interactions whilst the structure of the N-terminal region remains intact. © 2007 EBSA.
Author(s): Aisenbrey C, Sudheendra US, Ridley H, Bertani P, Marquette A, Nedelkina S, Lakey JH, Bechinger B
Publication type: Article
Publication status: Published
Journal: European Biophysics Journal
Year: 2007
Volume: 37
Issue: 1
Pages: 71-80
ISSN (print): 0175-7571
ISSN (electronic): 1432-1017
Publisher: Springer
URL: http://dx.doi.org/10.1007/s00249-007-0165-z
DOI: 10.1007/s00249-007-0165-z
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