Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E - The first three ligand-binding repeats of VtgR interact with the amino-terminal region on Vtg
Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E - The first three ligand-binding repeats of VtgR interact with the amino-terminal region on Vtg
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DOI：
10.1074/jbc.m205067200
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发表时间：
2003-01-31
影响因子：
4.8
通讯作者：
Ding, JL
中科院分区：
文献类型：
--
作者：
Li, AK;Sadasivam, M;Ding, JL
卵黄蛋白原受体（VtgR）属于低密度脂蛋白受体（LDLR）基因家族。它在卵生动物卵母细胞发育过程中介导卵黄蛋白原（Vtg）的摄取。在本研究中，我们克隆并鉴定了两种形式的金黄色Oreochromis aureus VtgR。Northern分析显示VtgR在卵巢组织中特异性表达。然而，逆转录pcr表明，在非卵巢组织中存在微量的VtgR表达或LDLR的同源物。VtgR与极低密度脂蛋白受体高度同源。为了更好地了解配体结合域中相似结构模块结合不同配体的机制，我们使用酵母双杂交系统筛选了Vtg和VtgR中最小相互作用基序。Vtg的脂磷脂I结构域的氨基末端区域与VtgR的配体结合结构域相互作用。发现受体的前三个配体结合重复序列对配体结合至关重要。结合序列的计算分析表明，Vtg与载脂蛋白（apo） E和载脂蛋白ob具有相似的受体结合区。该区域的定点突变表明Vtg与其受体之间存在静电相互作用。序列分析表明LDLR/apo超家族的受体-配体对共同进化，LDLR/极低密度脂蛋白受体与载脂蛋白ob和载脂蛋白e的结合方式继承自VtgR和Vtg的静电吸引。
The vitellogenin receptor (VtgR) belongs to the low density lipoprotein receptor (LDLR) gene family. It mediates the uptake of vitellogenin (Vtg) in oocyte development of oviparous animals. In this study, we cloned and characterized two forms of Oreochromis aureus VtgR. Northern analysis showed that VtgR was specifically expressed in ovarian tissues. However, reverse transcription-PCR indicates that either there are trace levels of expression of VtgR or a homolog of LDLR exists in nonovarian tissues. The VtgR is highly homologous to the very low density lipoprotein receptor. To better understand the mechanism by which similar structural modules in the ligand-binding domain bind different ligands, we used the yeast two-hybrid system to screen for the minimal interaction motifs in Vtg and VtgR. The amino-terminal region of the lipovitellin I domain of Vtg interacts with the ligand-binding domain of VtgR. The first three ligand-binding repeats of the receptor were found to be essential for ligand binding. Computational analysis of the binding sequence indicates that Vtg has a similar receptor-binding region to apolipoprotein (apo) E and apoB. Site-directed mutagenesis of this region indicates electrostatic interaction between Vtg and its receptor. Sequence analysis suggests the coevolution of receptor-ligand pairs for the LDLR/apo superfamily and suggests that the mode of binding of LDLR/very low density lipoprotein receptor to apoB and apoE is inherited from the electrostatic attraction of VtgR and Vtg.