Molecular characterization of a novel human hybrid-type receptor that binds the alpha(2)-macroglobulin receptor-associated protein
Molecular characterization of a novel human hybrid-type receptor that binds the alpha(2)-macroglobulin receptor-associated protein
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DOI：
10.1074/jbc.271.49.31379
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发表时间：
1996-12-06
影响因子：
4.8
通讯作者：
Petersen, CM
中科院分区：
文献类型：
--
作者：
Jacobsen, L;Madsen, P;Petersen, CM
39-40 kda受体相关蛋白（RAP）与低密度脂蛋白受体基因家族成员结合，是一种特化的内质网/高尔基蛋白伴侣。利用RAP亲和层析技术，我们纯化了一种与250 kda相似的新型脑蛋白，并分离了相应的cDNA。该基因被命名为SORL1，定位于11q23 /24号染色体，编码一个2214残基的1型受体，该受体在纯化蛋白中确定的N端之前含有一个furin切割位点。该受体被命名为sorLA-1，其胞质尾部较短，包含一个以酪氨酸为基础的内化信号，外部部分较大，包含（来自n端）：1)一个与酵母空泡蛋白分选10蛋白Vps10p结构域同源的片段，与羧肽酶Y结合；2)5个串联排列的YWTD重复序列和11个低密度脂蛋白受体基因家族受体特征的a类重复序列；3)6个串联排列的纤维连接蛋白III型重复序列也存在于某些神经粘附蛋白中。因此，sorLA-1可能被归类为一种杂交受体，Northern blotting在脑、脊髓和睾丸中发现了特定的mRNA转录物，但在几个主要器官中却没有。RAP和一种针对成熟蛋白序列的合成肽的抗体在粗人脑提取物中检测到sorLA-1。结构域结构表明sorLA-1是一种内吞受体，可能与脂蛋白和蛋白酶的摄取有关。
The 39-40-kDa receptor-associated protein (RAP) binds to the members of the low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone, Using RAP affinity chromatography, we have purified a novel similar to 250-kDa brain protein and isolated the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine-based internalization signal and a large external part containing (from the N-terminal): 1) a segment homologous to domains in the yeast vacuolar protein sorting 10 protein, Vps10p, that binds carboxypeptidase Y, 2) five tandemly arranged YWTD repeats and a cluster of 11 class A repeats characteristic of the low density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor, Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis but not in several major organs, Both RAP and an antibody against a synthetic peptide derived from a sequence determined in the mature protein detected sorLA-1 in crude human brain extracts. The domain structure suggests that sorLA-1 is an endocytic receptor possibly implicated in the uptake of lipoproteins and of proteases.