On the binding preference of human groups IIA and X phospholipases A2 for membranes with anionic phospholipids
On the binding preference of human groups IIA and X phospholipases A2 for membranes with anionic phospholipids
复制标题
DOI：
10.1074/jbc.m203137200
复制
发表时间：
2002-12-13
影响因子：
4.8
通讯作者：
Gelb, MH
中科院分区：
文献类型：
--
作者：
Bezzine, S;Bollinger, JG;Gelb, MH
哺乳动物含有9-10种分泌型磷脂酶A（2）（sPLA（2）s），它们对膜的亲和力因磷脂组成而异。与人类II A组sPLA（2）（hGIIA）相比，人类X组sPLA（2）（hGX）对富含磷脂酰胆碱（PC）的囊泡的酶活性要高得多，这在很大程度上是由于前者酶对此类囊泡的亲和力更高;当囊泡含有胆固醇和鞘磷脂时，这一结果也成立。在PC囊泡中包含阴离子磷脂酰丝氨酸显著增强了hGILA但不是hGX的界面结合和催化。这是大量赖氨酸和精氨酸残基分散在hGIIA的整个表面上的结果，这导致酶形成具有多个囊泡的超分子聚集体。因此，hGIIA与阴离子囊泡的高亲和力结合是一个复杂的过程，并且不能归因于其界面结合表面上的一些碱性残基，这也从诱变研究中显而易见。hGIIA与富含PC的囊泡结合不良的主要原因是其界面结合表面上缺乏色氨酸残基，该残基有助于hGX与富含PC的囊泡的高亲和力结合。结果表明，在PC囊泡的水解hGIIA的发病滞后部分是由于这些囊泡的这种酶的亲和力差。hGIIA、hGX及其突变体对富含PC的囊泡的结合亲和力与这些酶作用于哺乳动物细胞富含PC的外质膜的能力密切相关。
Mammals contain 9-10 secreted phospholipases A(2) (sPLA(2)s) that display widely different affinities for membranes, depending on the phospholipid composition. The much higher enzymatic activity of human group X sPLA(2) (hGX) compared with human group IIA sPLA(2) (hGIIA) on phosphatidylcholine (PC)-rich vesicles is due in large part to the higher affinity of the former enzyme for such vesicles; this result also holds when vesicles contain cholesterol and sphingomyelin. The inclusion of anionic phosphatidylserine in PC vesicles dramatically enhances interfacial binding and catalysis of hGILA but not of hGX. This is the result of the large number of lysine and arginine residues scattered over the entire surface of hGIIA, which cause the enzyme to form a supramolecular aggregate with multiple vesicles. Thus, high affinity binding of hGIIA to anionic vesicles is a complex process and cannot be attributed to a few basic residues on its interfacial binding surface, as is also evident from mutagenesis studies. The main reason hGIIA binds poorly to PC-rich vesicles is that it lacks a tryptophan residue on its interfacial binding surface, a residue that contributes to the high affinity binding of hGX to PC-rich vesicles. Results show that the lag in the onset of hydrolysis of PC vesicles by hGIIA is due in part to the poor affinity of this enzyme for these vesicles. Binding affinity of hGIIA, hGX, and their mutants to PC-rich vesicles is well correlated to the ability of these enzymes to act on the PC-rich outer plasma membrane of mammalian cells.