POSITIVELY CHARGED RESIDUES ARE IMPORTANT DETERMINANTS OF MEMBRANE-PROTEIN TOPOLOGY
POSITIVELY CHARGED RESIDUES ARE IMPORTANT DETERMINANTS OF MEMBRANE-PROTEIN TOPOLOGY
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DOI：
10.1016/0968-0004(90)90047-f
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发表时间：
1990-07-01
影响因子：
13.8
通讯作者：
DALBEY, RE
中科院分区：
文献类型：
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作者：
DALBEY, RE
有越来越多的实验证据表明，正电荷在决定蛋白质的膜取向中发挥作用。各种整合序列的序列比较研究提供了第一个证据。碱性残基通常位于前导肽的氨基末端，在羧基末端侧很少。前导肽的这种电荷不平衡也经常在未切割信号中观察到，特别是如果它们位于蛋白质分子的氨基末端。对于几种蛋白质2-15，前导肽的碱性氨基末端对于蛋白质的快速输出是必需的，但对于蛋白质跨膜的易位似乎不是绝对必需的。最近，有几个报告表明，引入正电荷的羧基末端侧的前导肽膜插入有有害的影响。Beckwith和同事6表明，碱性磷酸酶前导肽下游的一个带正电荷的残基严重影响了它向周质的输出。E.螺旋OmpF-Lpp嵌合蛋白，其具有不可切割的肽Z、β-内酰胺酶13、17和前OmpA（HY Zhu，A. Kuhn和RE Dalbey，未出版）。这些数据表明，膜内的疏水结构域的方向可能会受到两侧的碱性残基的影响。带正电荷的残基，遵循疏水结构域有助于它的氨基末端面向周质的方向。疏水片段之前的正电荷倾向于定向跨膜片段，其羧基末端暴露于周质。
There is mounting experimental evidence suggesting that positive charges play a role in determining a protein's membrane orientation. Sequence comparison studies of the various integration sequences~ provided the first evidence. Basic residues are typically located at the amino terminus of leader peptides and are rare at the carboxyterminal side. This charge imbalance of leader peptides is also often observed for uncleaved signals, especially if they are located at the amino terminus of the protein molecule. For several proteins 2-15, the basic amino terminus of leader peptides is necessary for rapid protein export but does not appear to be absolutely essential for translocation of a protein across the membrane. More recently, there have been several reports demonstrating that the introduction of positive charges to the carboxy-terminal side of the leader peptide have deleterious affects on membrane insertion. Beckwith and colleagues 6 showed that a positively charged residue downstream of the leader peptide of alkaline phosphatase severely affected its export to the periplasm. Similar results were also obtained for the E. coil OmpF-Lpp chimeric protein possessing an uncleavable peptide z,[3-1actamase 13'17 and pro-OmpA (HY Zhu, A. Kuhn and RE Dalbey, unpublished). These data suggest that the orientation of a hydrophobic domain within the membrane may be influenced by the basic residues that flank it. Positively charged residues that follow a hydrophobic domain help orient it with its amino terminus facing the periplasm. Positive charges that precede a hydrophobic segment tend to orient the transmembrane segment with its carboxyl terminus exposed to the periplasm.