COMPLETE CLONING AND SEQUENCING OF RAT GP330 MEGALIN, A DISTINCTIVE MEMBER OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE FAMILY
COMPLETE CLONING AND SEQUENCING OF RAT GP330 MEGALIN, A DISTINCTIVE MEMBER OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE FAMILY
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DOI：
10.1073/pnas.91.21.9725
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
FARQUHAR, MG
中科院分区：
文献类型：
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作者：
SAITO, A;PIETROMONACO, S;FARQUHAR, MG
我们完成了大鼠Heymann肾炎的主要肾小球抗原gp 330的cDNA克隆和测序。推测的4660-aa序列，预期构成M（r）516，715的成熟蛋白，由可能的N-末端信号肽序列（25 aa）、胞外区（4400 aa）、单个跨膜结构域（22 aa）和C-末端胞质尾（213 aa）组成，胞外区含有低密度脂蛋白受体（LDLR）基因家族特有的三种类型的富含半胱氨酸的重复序列-形成四簇推定的配体结合结构域的36个LDLR配体结合重复序列，由8个YWTD间隔区分隔的16个生长因子重复序列和1个C-末端表皮生长因子重复序列。胞质尾含有两个拷贝的（FX）NPXY蛾，这代表了一个信号包被坑介导的内化和一个额外的类似蛾。gp 330的总体结构与LDL R相关蛋白（LRP）/α（2）-巨球蛋白受体相似，与线虫蛋白（报告为LRP的同源物）的相似性更高。然而，gp 330与这些蛋白质的不同之处在于：（i）在细胞外N末端和C末端区域发现的富含半胱氨酸的重复排列，（ii）YWTD间隔区中半胱氨酸残基的分布模式，（iii）RX（K/R）的位置弗林蛋白酶（一种前体加工内切蛋白酶）的R共识识别序列，以及（iv）胞质尾部的长度和结构。我们建议将gp 330命名为megalin（来自希腊语mega），这是迄今为止在脊椎动物中发现的最大的质膜蛋白。该cDNA的克隆将有助于研究gp 330/megalin的生理功能，并确定其在Heymann肾炎中的作用。
We completed the cDNA cloning and sequencing of gp330, the major kidney glomerular antigen for rat Heymann nephritis. The deduced 4660-aa sequence, expected to constitute a mature protein of M(r) 516,715, consists of a probable N-terminal signal peptide sequence (25 aa), an extracellular region (4400 aa), a single transmembrane domain (22 aa), and a C-terminal cytoplasmic tail (213 aa), The extracellular region contains three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) gene family-36 LDLR ligand-binding repeats forming four clusters of putative ligand-binding domains, 16 growth factor repeats separated by 8 YWTD spacer regions, and 1 C-terminal epidermal growth factor repeat. The cytoplasmic tail contains two copies of the (FX)NPXY moth, which represents a signal for coated pit-mediated internalization and an additional similar moth. The overall structure of gp330 is similar to that of the LDLR-related protein (LRP)/alpha(2)-macroglobulin receptor and shows even greater similarity to the Caenorhabditis elegans protein, reported as a homologue of LRP. However, gp330 differs from these proteins in (i) the cysteine-rich repeat arrangements found in the extreme extracellular N- and C-terminal regions, (ii) the distribution pattern of cysteine residues in the YWTD spacer regions, (iii) the location of the RX(K/R)R consensus recognition sequence of furin, a precursor processing endoprotease, and (iv) the length and structure of the cytoplasmic tail. We suggest the name megalin (from Greek mega) for gp330, the largest plasma membrane protein identified so far in vertebrates. The cloned cDNA will be useful for studies on the physiological functions of gp330/megalin and for determining its role in Heymann nephritis.