Principles for Topogenesis of Multispanning Membrane Proteins on Bio-membranes

生物膜上多跨膜蛋白的拓扑发生原理

• 批准号: 11480168
• 负责人: SAKAGUCHI Masao
• 金额: $ 9.6万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480168/
• 关键词: endoplasmic reticulum; mitochondria; topology; membrane protein; signal sequence; protein structure; 膜透過; 受容体; 生体膜; タンパク質膜透過

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).

该项目的主要目标是揭示各种膜蛋白的新生多肽链正确插入各种生物膜的所有模式，(1)阐明膜蛋白对线粒体外膜的靶向信号(Horie等人，MBC，2002；Kanaji等人，JCB，2000)。(2)我们发现，在I型(Nout/Ccyto)信号锚序列的拓扑发生过程中，位于氨基末端和疏水段之间的氨基酸残基具有高转角倾向性(Kida等人，FEBS Lett，2001；Kida等人，JCB，2000)。(3)我们证明了NHE6蛋白具有内质网膜信号肽(Miyazaki et al，JBC，2001)。(4)阐明了KAT1钾通道的拓扑发生模式，发现了高电荷跨膜段(S4)与内质网膜整合的新的拓扑发生模式(Sato等，PNAS，2002)。(5)证明了AtHKT1的一个新的拓扑模型--钾转运体，该模型中有四个“跨膜孔”单元结构(Kato et al，2001，PNAS)。(6)我们发现了紧密相对的跨膜片段的新的拓扑发生模式(Ukaji等人，BBRC，2002；Ota等人，JBC，2000)。(7)我们证明了阿尔茨海默病相关早老素1的新拓扑模型(Nakai等人，1999，JBC)。

项目成果

Miyazaki, B. et al.: "NHE6 protein possesses a signal peptide destined for endoplasmic reticulum membrane and localizes in secretory organelles of the cell"J. Biol. Chem.. 276. 49221-49227 (2001)

Miyazaki, B. 等人：“NHE6 蛋白拥有一个发往内质网膜的信号肽，并定位于细胞的分泌细胞器中”J.

Horie, C., Suzuki, H., Sakaguchi, M. & Mihara, K.: "Characterization of the signal that directs the C-tail anchored proteins to the mammalian mitochondrial outer membrane"Mol. Biol. Cell. 13 (in press). (2002)

堀江，C.，铃木，H.，坂口，M.

Kato, Y.et al.: "Evidence in support of a four transmembrane-pore-transmembrane topology model for the arabidopsis thaliana Na^+/K^+ translocating AtHKT1 protein, a member of the superfamily of K^+ transporters"Proc.Natl.Acad.Sci.USA. 98. 6488-6493 (2001)

Kato, Y. 等人：“支持拟南芥 Na^ /K^ 易位 AtHKT1 蛋白（K^ 转运蛋白超家族成员）的四跨膜-孔-跨膜拓扑模型的证据”Proc.Natl.Acad

Kusano, K. et al.: "Importance of a proline-rich sequence in the amino-terminal region for correct folding of mitochondrial and soluble microbial P45Os"J. Biochem.. 129. 271-277 (2001)

Kusano, K. 等人：“氨基末端区域富含脯氨酸的序列对于线粒体和可溶性微生物 P45O 正确折叠的重要性”J.

Sato, Y. et al.: "Integration of Shaker-typeK^+ channel, KAT1 into the endoplasmic reticulum membrane : Synergistic insertion of voltage sensing segments, S3-S4 and independent insertion of pore-forming segments, S5-P-S6"Proc. Nati. Acad. Sci. USA. 99. 60

Sato, Y. 等人：“将 Shaker 型 K^ 通道、KAT1 整合到内质网膜中：电压传感片段 S3-S4 的协同插入和成孔片段 S5-P-S6 的独立插入”Proc