Lambeau G, Ancian P, Nicolas J P, Beiboer S H, Moinier D, Verheij H, Lazdunski M
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
J Biol Chem. 1995 Mar 10;270(10):5534-40. doi: 10.1074/jbc.270.10.5534.
Specific membrane receptors for secretory phospholipases A2 (sPLA2s) have been initially identified with novel snake venom sPLA2s called OS1 and OS2. One of these sPLA2 receptors (muscle (M)-type, 180 kDa) has a very high affinity for OS1 and OS2 and a high affinity for pancreatic and inflammatory-type mammalian sPLA2s, which might be the natural endogenous ligands of PLA2 receptors. Primary structures of OS1 and OS2 were determined and compared with sequences of other sPLA2s that bind less tightly or do not bind to the M-type receptor. In addition, the binding properties of pancreatic sPLA2 mutants to the M-type receptor have been analyzed. Residues within or close to the Ca(2+)-binding loop of pancreatic sPLA2 are crucially involved in the binding step, although the presence of Ca2+ that is essential for the enzymatic activity is not required for binding to the receptor. These residues include Gly-30 and Asp-49, which are conserved in all sPLA2s. Leu-31 is also essential for binding of pancreatic sPLA2 to its receptor. Many other mutations have been considered. Those occurring in the N-terminal alpha helices and the pancreatic loop do not change binding to the M-type receptor. Conversion of pancreatic prophospholipase to phospholipase is essential for the acquisition of binding properties to the M-type receptor.
分泌型磷脂酶A2（sPLA2s）的特异性膜受体最初是通过名为OS1和OS2的新型蛇毒sPLA2s鉴定出来的。其中一种sPLA2受体（肌肉（M）型，180 kDa）对OS1和OS2具有非常高的亲和力，对胰腺型和炎症型哺乳动物sPLA2s具有高亲和力，而这些可能是PLA2受体的天然内源性配体。确定了OS1和OS2的一级结构，并与其他与M型受体结合较松或不结合的sPLA2s序列进行了比较。此外，还分析了胰腺sPLA2突变体与M型受体的结合特性。胰腺sPLA2的Ca（2+）结合环内或附近的残基在结合步骤中起关键作用，尽管酶活性所必需的Ca2+的存在对于与受体的结合不是必需的。这些残基包括Gly-30和Asp-49，它们在所有sPLA2s中都是保守的。Leu-31对于胰腺sPLA2与其受体的结合也至关重要。还考虑了许多其他突变。那些发生在N端α螺旋和胰腺环中的突变不会改变与M型受体的结合。胰腺前磷脂酶转化为磷脂酶对于获得与M型受体的结合特性至关重要。
