A cholesterol recognition motif in human phospholipid scramblase 1

POSADA, I.M.; FANTINI, J.; CONTRERAS, F.X.; BARRANTES, F.J.; ALONSO, A.; GOÑI, F.M.

BIOPHYSICAL JOURNAL

CELL PRESS

Lugar: United States; Año: 2014 vol. 107 p. 1383 - 1392

0006-3495

Human phospholipid scramblase 1 (SCR) catalyzes phospholipid transmembrane (flip-flop) motion. This protein is assumed to bind the membrane hydrophobic core through a transmembrane domain (TMD) as well as via covalently bound palmitoyl residues. Here, we explore the possible interaction of the SCR TMD with cholesterol by using a variety of experimental and computational biophysical approaches. Our findings indicate that SCR contains an amino acid segment at the C-terminal region that shows a remarkable affinity for cholesterol, although it lacks the CRAC sequence. Other 3-OH sterols, but not steroids lacking the 3-OH group, also bind this region of the protein. The newly identified cholesterol-binding region is located partly at the C-terminal portion of the TMD and partly in the first amino acid residues in the SCR C-terminal extracellular coil. This finding could be related to the previously described affinity of SCR for cholesterol-rich domains in membranes.