國家衛生研究院 NHRI:Item 3990099045/5908
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    题名: Proline in transmembrane domain of type II protein DPP-IV governs Its translocation behavior through endoplasmic reticulum
    作者: Chung, KM;Huang, CH;Cheng, JH;Tsai, CH;Suen, CS;Hwang, MJ;Chen, X
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: A transmembrane domain (TMD) at the N-terminus of a membrane protein is a signal sequence that targets the protein to the endoplasmic reticulum (ER) membrane. Proline is found more frequently in TM helices compared to water-soluble helices. To investigate the effects of proline on protein translocation and integration in mammalian cells, we made proline substitutions throughout the TMD of dipeptidyl peptidase IV, a type II membrane protease with a single TMD at its N-terminus. The proteins were expressed and their capacities for targeting and integrating into the membrane were measured in both mammalian cells and in vitro translation systems. Three proline substitutions in the central region of the TMD resulted in various defects in membrane targeting and/or integration. The replacement of proline with other amino acids of similar hydrophobicity rescued both the translocation and anchoring defects of all three proline mutants, indicating that conformational change caused by proline is a determining factor. Increasing hydrophobicity of the TMD by replacing other residues with more hydrophobic residues also effectively reversed the translocation and integration defects. Intriguingly, increasing hydrophobicity at the C-terminal end of the TMD rescued much more effectively than it did at the N-terminal end. Thus, the effect of proline on translocation and integration of the TMD is not determined solely by its conformation and hydrophobicity, but also by the location of proline in the TMD, the location of highly hydrophobic residues, and the relative position of the proline to other proline residues in the TMD.
    日期: 2011-09
    關聯: Biochemistry. 2011 Sep;50(37):7909-7918.
    Link to: http://dx.doi.org/10.1021/bi200605h
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2960&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000294791100008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80052746513
    显示于类别:[陳新(2002-2015)] 期刊論文

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