Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization.
Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization.
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DOI：
10.1038/nm1179
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发表时间：
2005-03
期刊：
影响因子：
82.9
通讯作者：
Takeda J
中科院分区：
文献类型：
--
作者：
Kondoh G;Tojo H;Nakatani Y;Komazawa N;Murata C;Yamagata K;Maeda Y;Kinoshita T;Okabe M;Taguchi R;Takeda J
血管紧张素转换酶（ACE）是血压的关键调节因子。已知它切割小肽，如血管紧张素I和缓激肽，并改变其生物活性，导致血压上调。在这里，我们描述了一个新的活动ACE：糖基磷脂酰肌醇（GPI）锚定蛋白释放活性（GPIase活性）。与其肽酶活性不同，GPIase活性被紧密结合的ACE抑制剂弱抑制，并且不被肽酶活性的核心氨基酸残基的取代灭活，这表明GPIase的活性位点元素不同于肽酶活性的那些。ACE从细胞表面脱落各种GPI锚定蛋白，并且该过程被脂筏破坏剂filipin加速。释放的产物携带GPI锚的部分，表明GPI部分内的裂解。通过高效液相色谱-质谱法的进一步分析预测了甘露糖-甘露糖键的裂解位点。GPI锚定蛋白如TESP 5和PH-20从野生型小鼠的精子膜中释放，但在体内Ace敲除精子中不释放。此外，肽酶失活的E414 D突变体ACE和PI-PLC拯救了Ace敲除精子的卵子结合缺陷，这意味着ACE通过这种活动在受精中起着至关重要的作用。本文的在线版本（doi：10.1038/nm 1179）包含补充材料，可供授权用户使用。
The angiotensin-converting enzyme (ACE) is a key regulator of blood pressure. It is known to cleave small peptides, such as angiotensin I and bradykinin and changes their biological activities, leading to upregulation of blood pressure. Here we describe a new activity for ACE: a glycosylphosphatidylinositol (GPI)-anchored protein releasing activity (GPIase activity). Unlike its peptidase activity, GPIase activity is weakly inhibited by the tightly binding ACE inhibitor and not inactivated by substitutions of core amino acid residues for the peptidase activity, suggesting that the active site elements for GPIase differ from those for peptidase activity. ACE shed various GPI-anchored proteins from the cell surface, and the process was accelerated by the lipid raft disruptor filipin. The released products carried portions of the GPI anchor, indicating cleavage within the GPI moiety. Further analysis by high-performance liquid chromatography–mass spectrometry predicted the cleavage site at the mannose-mannose linkage. GPI-anchored proteins such as TESP5 and PH-20 were released from the sperm membrane of wild-type mice but not in Ace knockout sperm in vivo. Moreover, peptidase-inactivated E414D mutant ACE and also PI-PLC rescued the egg-binding deficiency of Ace knockout sperms, implying that ACE plays a crucial role in fertilization through this activity. The online version of this article (doi:10.1038/nm1179) contains supplementary material, which is available to authorized users.
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DOI：
10.1083/jcb.125.5.1157
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lin Y;Mahan K;Lathrop WF;Myles DG;Primakoff P
通讯作者：
Primakoff P
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
4.8
作者：
Honda, A;Yamagata, K;Baba, T
通讯作者：
Baba, T
影响因子：
64.8
作者：
Natesh, R;Schwager, SLU;Acharya, KR
通讯作者：
Acharya, KR
影响因子：
64.8
作者：
Crackower, MA;Sarao, R;Penninger, JM
通讯作者：
Penninger, JM