A monomeric membrane peptide that lives in three worlds: In solution, attached to, and inserted across lipid bilayers
A monomeric membrane peptide that lives in three worlds: In solution, attached to, and inserted across lipid bilayers
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DOI：
10.1529/biophysj.107.109967
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Engelman, Donald M.
中科院分区：
文献类型：
--
作者：
Reshetnyak, Yana K.;Segala, Michael;Engelman, Donald M.
膜肽pH（低）插入肽（pHLIP）存在于三个世界中，在pH 7.4下可溶于水溶液，结合到脂质双层的表面，以及在低pH下作为跨双层螺旋插入。在低pH驱动该过程的情况下，pHLIP可以通过二硫化物转移附着到其C末端的货物分子，并将它们释放到细胞的细胞质中。在这里，我们研究了一个关键方面的机制，表明pHLIP是单体在其三个主要状态：可溶于水接近中性pH值（状态I），结合到表面的膜接近中性pH值（状态II），并插入在膜作为一个α-螺旋在低pH值（状态III）。该肽不诱导融合或膜渗漏。pHLIP的独特性质使其对体外膜蛋白折叠的生物物理研究和开发用于将治疗剂和诊断剂转运至与体内各种病理过程相关的酸性组织部位的新型递送肽类具有吸引力。
The membrane peptide pH (low) insertion peptide (pHLIP) lives in three worlds, being soluble in aqueous solution at pH 7.4, binding to the surface of lipid bilayers, and inserting as a transbilayer helix at low pH. With low pH driving the process, pHLIP can translocate cargo molecules attached to its C-terminus via a disulfide and release them in the cytoplasm of a cell. Here we examine a key aspect of the mechanism, showing that pHLIP is monomeric in each of its three major states: soluble in water near neutral pH (state I), bound to the surface of a membrane near neutral pH (state II), and inserted across the membrane as an alpha-helix at low pH (state III). The peptide does not induce fusion or membrane leakage. The unique properties of pHLIP made it attractive for the biophysical investigation of membrane protein folding in vitro and for the development of a novel class of delivery peptides for the transport of therapeutic and diagnostic agents to acidic tissue sites associated with various pathological processes in vivo.