脂类的特定激活小鼠P4-ATPase Atp8a1 (atp酶II)。

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帕特森JK, Renkema K, L,负担Halleck女士,Schlegel RA,威廉姆森P Daleke DL

脂类的特定激活小鼠P4-ATPase Atp8a1 (atp酶II)。

生物化学。2006年4月25日,45 (16):5367 - 76。

PubMed ID

16618126 (在PubMed

]

文摘

transbilayer不对称分布的磷脂酰丝氨酸(PS)在哺乳动物的质膜和分泌小泡,在某种程度上,ATP-dependent运输车。这aminophospholipid flippase选择性传输PS的胞质传单双层和钒酸敏感,Ca(2 +),通过巯基试剂和修改。虽然flippase没有验明正身,提出了p型atp酶的亚科函数作为amphipaths的转运蛋白,包括PS和其他磷脂。候选人PS flippase ATP8A1 (atp酶II),最初从牛分泌囊泡分离,属于该亚科基于序列同源性亚科的创始成员,酵母蛋白质Drs2,已与核糖体的组装、Golgi-coated囊泡的形成,和维护PS不对称。确定如果ATP8A1生化特性与PS flippase一致,这种酶的小鼠同系物在昆虫细胞表达和纯化。洗涤剂的纯化Atp8a1活性胶束或胶束含有磷脂酰胆碱,磷脂酸,或磷脂酰肌醇,具有最低限度激活phosphatidylglycerol或磷脂酰乙醇胺(PE),并最大限度地激活PS。PS的选择性是依赖于脂质结构的多个元素。类似于质膜PS运输机,由天然sn-1 Atp8a1只激活,2-glycerol异构体的PS和不是sn-2 3-glycerol立体异构体。flippase和Atp8a1活动都对丝氨酸headgroup的立体化学。大多数PS headgroup结构的修改由质膜PS flippase减少识别。激活Atp8a1也减少了这些修改; phosphatidylserine-O-methyl ester, lysophosphatidylserine, glycerophosphoserine, and phosphoserine, which are not transported by the plasma membrane flippase, do not activate Atp8a1. Weakly translocated lipids (PE, phosphatidylhydroxypropionate, and phosphatidylhomoserine) are also weak Atp8a1 activators. However, N-methyl-phosphatidylserine, which is transported by the plasma membrane flippase at a rate equivalent to PS, is incapable of activating Atp8a1 activity. These results indicate that the ATPase activity of the secretory granule Atp8a1 is activated by phospholipids binding to a specific site whose properties (PS selectivity, dependence upon glycerol but not serine, stereochemistry, and vanadate sensitivity) are similar to, but distinct from, the properties of the substrate binding site of the plasma membrane flippase.

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药物靶点

药物	目标	类	生物	药理作用	行动
磷脂酰丝氨酸	可能phospholipid-transporting腺苷三磷酸酶IA	蛋白质	人类	未知的	不可用	细节