Control of phospholipid flip-flop by transmembrane peptides

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• 作者：Masanori Kaihara^a ; Hiroyuki Nakao^a ; Hirokazu Yokoyama^a ; Hitoshi Endo^b ; Yasushi Ishihama^a ; Tetsurou Handa^c ; Minoru Nakano^d ; ^{mnakano@pha.u-toyama.ac.jp}
• 关键词：Phospholipid ; Flip-flop ; Transmembrane peptide ; Small-angle neutron scattering ; Fluorescence ; Dithionite assay
• 刊名：Chemical Physics
• 出版年：2013
• 出版时间：20 June, 2013
• 年：2013
• 卷：419
• 期：Complete
• 页码：78-83
• 全文大小：751 K

文摘

We designed three types of transmembrane model peptides whose sequence originates from a frequently used model peptide KALP23, and we investigated their effects on phospholipid flip-flop. Time-resolved small-angle neutron scattering and a dithionite fluorescent quenching assay demonstrated that TMP-L, which has a fully hydrophobic transmembrane region, did not enhance phospholipid flip-flop, whereas TMP-K and TMP-E, which have Lys and Glu, respectively, in the center of their transmembrane regions, enhanced phospholipid flip-flop. Introduction of polar residues in the membrane-spanning helices is considered to produce a locally polar region and enable the lipid head group to interact with the polar side-chain inside the bilayers, thereby reducing the activation energy for the flip-flop. A bioinformatics approach revealed that acidic and basic residues account for 4.5 % of the central region of the transmembrane domain in human ER membrane proteins. Therefore, polar residues in ER membrane proteins are considered to provide flippase-like activity.