The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule.

The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule.
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DOI:
10.1016/s0021-9258(18)54445-8
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发表时间:
1991-12
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
D. Noonan;Anna Fulle;Piera Valente;S. Cai;E. Horigan;M. Sasaki;Yoshihiko Yamada;J. Hassell
D. Noonan;Anna Fulle;Piera Valente;S. Cai;E. Horigan;M. Sasaki;Yoshihiko Yamada;J. Hassell
中科院分区:
其他
文献类型:
--
作者:
D. Noonan;Anna Fulle;Piera Valente;S. Cai;E. Horigan;M. Sasaki;Yoshihiko Yamada;J. Hassell

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硫酸乙酰肝素蛋白多糖是所有基底膜的一种成分。该分子由三个硫酸乙酰肝素侧链组成,与一个约400 kDa的大核心蛋白相连。我们已经分离到7个重叠的小鼠cDNA克隆,它们编码该分子12.685个碱基的整个mRNAs序列。该序列有一个由3707个氨基酸组成的单一开放阅读框架,编码一个396 kDa的蛋白质。与从Engelbreth-Holm-Sound肿瘤分离的分子核心蛋白衍生的9个肽序列相同或接近相同的配对与推导的序列一起被发现。序列分析和数据库比对表明,该蛋白质由5个不同的结构域组成,其中大部分含有内部重复序列。结构域I包含一个起始蛋氨酸,然后是一个典型的信号传递序列,以及一个由172个氨基酸组成的独特片段,该片段包含硫酸乙酰肝素结合的三个可能位置,SGD。结构域II包含四个富含半胱氨酸和酸性氨基酸的重复序列,它们与低密度脂蛋白受体和GP330等蛋白质中的重复序列非常相似。结构域III由富含半胱氨酸的区域和球状区域组成,这两个区域都与层粘连蛋白A链短臂上的区域相似。结构域IV包含免疫球蛋白超家族的14个重复序列,它们与神经细胞黏附分子中的免疫球蛋白样重复序列高度相似。结构域V包含三个与层粘连蛋白A链G结构域相似的重复序列,由层粘连蛋白A链中未发现的表皮生长因子样区分隔。由于初级结构数据与电子显微镜中分子的外观一致,因此我们将这种分子命名为Perlecan。Perlecan中结构域的多样性表明它与其他分子有多种相互作用。
A heparan sulfate proteoglycan is a component of all basement membranes. This molecule consists of three heparan sulfate side chains linked to a large core protein of approximately 400 kDa. We have isolated seven overlapping murine cDNA clones that encode the entire mRNA sequence of 12.685 kilobases of this molecule. This sequence has a single open reading frame of 3,707 amino acids that encodes for a protein of 396 kDa. Identical or near identical matchups with nine peptide sequences derived from the core protein of the molecule isolated from the Engelbreth-Holm-Swarm tumor were found with the deduced sequence. Sequence analysis and data base comparison of the deduced sequence show the protein to consist of five different domains, most of which contain internal repeats. Domain I contains a start methionine followed by a typical signal transfer sequence and a unique segment of 172 amino acids that contains the three probable sites of heparan sulfate attachment, SGD. Domain II contains four cysteine- and acidic amino acid-rich repeats that are very similar to those found in the LDL receptor and proteins such as GP330. Domain III consists of cysteine-rich and globular regions, both of which show similarity to those in the short arm of the laminin A chain. Domain IV contains 14 repeats of the immunoglobulin superfamily that are most highly similar to the immunoglobulin-like repeats in the neural cell adhesion molecule. Domain V contains three repeats with similarity to the laminin A chain G domain that are separated by epidermal growth factor-like regions not found in the laminin A chain. As the primary structural data agree with the appearance of the molecule in the electron microscope as a series of globules separated by rods, or “beads on a string,” we have adopted the name perlecan for this molecule. The variety of domains in perlecan suggest multiple interactions with other molecules.