N-terminal domain of apolipoprotein B has structural homology to lipovitellin and microsomal triglyceride transfer protein: a "lipid pocket" model for self-assembly of apob-containing lipoprotein particles.
N-terminal domain of apolipoprotein B has structural homology to lipovitellin and microsomal triglyceride transfer protein: a "lipid pocket" model for self-assembly of apob-containing lipoprotein particles.
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发表时间：
1999-08
影响因子：
6.5
通讯作者：
J. Segrest;Martin K. Jones;Nassrin Dashti
中科院分区：
文献类型：
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作者：
J. Segrest;Martin K. Jones;Nassrin Dashti
含载脂蛋白（apo）B的脂蛋白颗粒的组装过程发生在apoB N-末端结构域的二硫键依赖性折叠之后，但其机制尚不清楚。在最近的一次数据库搜索中，发现含有与apoB-100相似的两亲性β链的蛋白质序列，四种卵黄蛋白原，即卵黄脂蛋白（一种蛋黄脂蛋白）的前体形式，来自鸡、青蛙、七鳃鳗和C。秀丽线虫出现在候选蛋白质名单上。七鳃鳗卵黄脂磷蛋白的X射线晶体结构已知含有由反平行的两亲性β片层排列的“脂质口袋”。在这里，我们报告说，前1000个残基的人apoB-100（α（1）结构域加上前200个残基的β（1）结构域）具有序列和两亲性基序的七鳃鳗卵黄脂磷蛋白的脂质结合口袋同源。我们还发现，大多数人apoB-100的α（1）结构域的序列和两亲性基序同源性的人微粒体甘油三酯转移蛋白（MTP），一种蛋白质的装配载脂蛋白B-含有脂蛋白。基于这些结果，我们认为，左室样的“蛋白脂质”中间体含有“脂质口袋”是由单独的载脂蛋白B的N-末端部分，或更有可能，作为一个复杂的MTP。该中间体产生装配含apoB的脂蛋白颗粒所需的脂质巢;通过添加来自apoB的β（1）结构域的两亲性β链的口袋扩张导致形成逐渐变大的高密度脂蛋白（HDL）样、然后极低密度脂蛋白（VLDL）样球状脂蛋白颗粒。
The process of assembly of apolipoprotein (apo) B-containing lipoprotein particles occurs co-translationally after disulfide-dependent folding of the N-terminal domain of apoB but the mechanism is not understood. During a recent database search for protein sequences that contained similar amphipathic beta strands to apoB-100, four vitellogenins, the precursor form of lipovitellin, an egg yolk lipoprotein, from chicken, frog, lamprey, and C. elegans appeared on the list of candidate proteins. The X-ray crystal structure of lamprey lipovitellin is known to contain a "lipid pocket" lined by antiparallel amphipathic beta sheets. Here we report that the first 1000 residues of human apoB-100 (the alpha(1) domain plus the first 200 residues of the beta(1) domain) have sequence and amphipathic motif homologies to the lipid-binding pocket of lamprey lipovitellin. We also show that most of the alpha(1) domain of human apoB-100 has sequence and amphipathic motif homologies to human microsomal triglyceride transfer protein (MTP), a protein required for assembly of apoB-containing lipoproteins. Based upon these results, we suggest that an LV-like "proteolipid" intermediate containing a "lipid pocket" is formed by the N-terminal portion of apoB alone or, more likely, as a complex with MTP. This intermediate produces a lipid nidus required for assembly of apoB-containing lipoprotein particles; pocket expansion through the addition of amphipathic beta strands from the beta(1) domain of apoB results in the formation of a progressively larger high density lipoprotein (HDL)-like, then very low density lipoprotein (VLDL)-like, spheroidal lipoprotein particle.