Fig. 4. Three cardiolipin molecules are tightly bound to UCP1.

(A) Endogenous cardiolipin co-purifies with UCP1, as shown by the detection of unsaturated lipid, specifically, following thin layer chromatography of lipid extracts from purified UCP1 after 300 mL washes in decylmaltoside supplemented with GDP plus 14:0 phosphatidylcholine (1) or 14:0 cardiolipin (2) [36]. (B) Lateral view of the yeast ADP/ATP carrier Aac2p showing binding of three cardiolipin molecules CDL800 (light blue), CDL801 (grey) and CDL802 (green) [105]. The protein and cardiolipin molecules are shown in cartoon and ball-and-stick representations, respectively. The cardiolipin acyl chains have only been partially modelled. (C) Detailed view of the binding site for cardiolipin molecule CDL801. Hydrogen bonds within the helices are shown as thin black dotted lines. Residues in the [YWF][KR]G and [YF]XG motifs are shown in violet and green, respectively. Hydrogen bond interactions between protein and cardiolipin are shown as thick cyan dashed lines. The positive and negative helical dipole are shown in blue and red, respectively. (D), (E), and (F) amino acid sequences of the cardiolipin binding sites of CDL800, CDL801, and CDL802, respectively, of the mitochondrial ADP/ATP carrier and uncoupling protein from the following species: Bt, Bos taurus; Hs, Homo sapiens; Sc, Saccharomyces cerevisiae; Ml, Myotis lucifugus; Cf, Canis familiaris; Et, Echinops telfairi; Rn, Rattus norvegicus; Mm, Mus musculus; Dg, Dicrostonyx groenlandicus; Ma, Mesocricetus auratus; Ps, Phodopus sungorus; Oa, Ovis aries; Bb, Bubalus bubalis; Oc, Oryctolagus cuniculus; Od, Ochotona dauurica; Og, Otolemur garnettii and Pt, Pan troglodytes.