Principles for Topogenesis of Multispanning Membrane Proteins on Bio-membranes

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The major objective of this project is to uncover all of the modes via which nascent polypeptide chains of various membrane proteins are correctly inserted into various bio-membranes, (1) The targeting signals of the membrane proteins to the mitochondrial outer membrane are elucidated (Horie et al, MBC, 2002 ; Kanaji et al, JCB, 2000). (2) We found the importance of amino acid residues with high turn propensity scale between amino-terminal domain and the hydrophobic segment for the topogenesis of type I (Nout/Ccyto) signal-anchor sequence (Kida et al, FEBS Lett, 2001 ; Kida et al, JCB, 2000). (3) We demonstrated that NHE6 protein possesses signal peptide destined for the endoplasmic reticulum membrane (Miyazaki et al, JBC, 2001). (4) We clarified the topogenic modes of KAT1, potassium channel, and found novel topogenic one for membrane integration of highly charged transrnembrane segment (S4) into endoplasmic reticulum membrane (Sato et al, PNAS, 2002). (5) We proved the novel topology model of AtHKT1, potassium transporter, in which there are four "transmembrane pore transmembrane" unit structures (Kato et al, 2001, PNAS). (6) We found novel topogenic mode for closely apposed transmembrane segments (Ukaji et al, BBRC, 2002 ; Ota et al, JBC, 2000). (7) We demonstrated the novel topology model of Alzheimer's disease-related presenilin 1 (Nakai et al, 1999, JBC).