PARTIAL AMINO-ACID-SEQUENCE OF APOLIPOPROTEIN(A) SHOWS THAT IT IS HOMOLOGOUS TO PLASMINOGEN
PARTIAL AMINO-ACID-SEQUENCE OF APOLIPOPROTEIN(A) SHOWS THAT IT IS HOMOLOGOUS TO PLASMINOGEN
复制标题
DOI：
10.1073/pnas.84.10.3224
复制
发表时间：
1987-05-01
影响因子：
11.1
通讯作者：
SCANU, AM
中科院分区：
文献类型：
--
作者：
EATON, DL;FLESS, GM;SCANU, AM
载脂蛋白（a）[apo（a）]是一种Mr约280，000的糖蛋白，它与脂蛋白（a）颗粒中的载脂蛋白B二硫键连接.血浆脂蛋白（a）水平升高与动脉粥样硬化相关。apo（a）的部分氨基酸序列与纤溶酶原有显著的同源性。纤溶酶原是一种血浆丝氨酸蛋白酶酶原，由五个同源和串联重复的结构域（称为Kringles）和一个胰蛋白酶样蛋白酶结构域组成。apo（a）的氨基末端序列与kringle 4的起始部分同源，但与纤溶酶原的氨基末端不同。通过胰蛋白酶或V8蛋白酶对Apo（a）进行有限的蛋白水解，分离产生的片段并测序。从这些片段中的几个获得的序列与位于Kringle 4内的纤溶酶原残基391-421高度（77-100%）同源。对这些内部载脂蛋白（a）序列的分析表明，载脂蛋白（a）可能含有至少两个kringle 4样结构域。从另一个胰蛋白酶片段获得的序列也显示出与Kringle 4的末端和Kringle 5的开始同源。从两个胰蛋白酶片段获得的序列数据显示与纤溶酶原的蛋白酶结构域同源。这些序列之一与纤溶酶原激活位点周围的序列同源。纤溶酶原通过尿激酶和组织纤溶酶原激活剂切割特定精氨酸残基而激活;然而，apo（a）中丝氨酸中的相应位点不会被组织纤溶酶原激活剂或尿激酶切割。使用纤溶酶特异性测定，脂蛋白（a）颗粒未显示蛋白水解活性。这些结果表明，载脂蛋白（a）含有kringle样结构域和一个无活性的蛋白酶结构域。
Apolipoprotein(a) [apo(a)] is a glycoprotein with Mr .apprxeq.280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from two tryptic fragments show homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) in a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain.