title: Membrane promotes tBID interaction with BCL(XL).
abstract: Two important questions on the molecular mechanism of the B cell CLL/lymphoma 2 (BCL2) proteins involve the interaction network between pro- and antiapoptotic members and the role of their translocation to the mitochondrial membrane during apoptosis. We used fluorescence correlation spectroscopy to quantify the molecular interactions of BH3-interacting domain death agonist (BID) and its truncated form tBID with the B cell lymphoma extra-large protein truncated at the C terminus (BCL(XL)DeltaCt) in solution and in membranes, and we found that (i) only the active form tBID binds to BCL(XL)DeltaCt and (ii) that the membrane strongly promotes binding between them. Particularly, a BH3 peptide from BID disrupts the tBID-BCL(XL) complex in solution, but only partially in lipid bilayers. These data indicate that tBID-BCL(XL) interactions in solution and lipid membranes are distinct, and they support a model in which BCL(XL) inhibition of tBID takes place predominantly at the membrane. Our findings imply an active role of the membrane in modulating the interactions between BCL2 proteins that has so far been underestimated.
authors.affiliation: Biophysics Group, BIOTEC, TU Dresden, Dresden, Germany. ana.garcia@biotec.tu-dresden.de
authors.forename: Ana J
authors.initials: AJ
authors.lastname: García-Sáez
authors.forename: Jonas
authors.initials: J
authors.lastname: Ries
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payà
authors.forename: Petra
authors.initials: P
authors.lastname: Schwille
mesh_terms: D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008566:Membranes / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D051020:bcl-X Protein