VARIANTS OF THE CELL RECOGNITION SITE OF FIBRONECTIN THAT RETAIN ATTACHMENT-PROMOTING ACTIVITY
VARIANTS OF THE CELL RECOGNITION SITE OF FIBRONECTIN THAT RETAIN ATTACHMENT-PROMOTING ACTIVITY
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DOI：
10.1073/pnas.81.19.5985
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
RUOSLAHTI, E
中科院分区：
文献类型：
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作者：
PIERSCHBACHER, MD;RUOSLAHTI, E
四肽序列Arg-Gly-Asp-Ser是细胞识别的大的粘附糖蛋白纤连蛋白中的最小结构。通过测试活性四肽序列的几种合成变体来定义该细胞识别位点的结构要求。赖氨酸取代精氨酸，丙氨酸取代甘氨酸，或谷氨酸取代天冬氨酸的保守取代各自导致天然序列的细胞附着促进活性特征的废除。在丝氨酸残基的位置，一些改变与活性相容。对含有Arg-Gly-Asp-X（其中X =另一个氨基酸残基）结构的肽的分析表明，由于替代性RNA剪接，预测存在于一些但不是全部纤连蛋白分子中的Arg-Gly-Asp-Val序列可能在携带该序列的纤连蛋白多肽链中产生第二个细胞附着位点。具有潜在活性Arg-Gly-Asp-X序列的其他蛋白质包括已知与细胞表面相互作用的几种蛋白质。其中包括各种类型的胶原蛋白、凝血酶和盘状蛋白，盘状蛋白是一种可能参与细胞聚集的黏菌蛋白。精氨酸、甘氨酸和天冬氨酸残基是细胞识别所绝对需要的，并且周围的氨基酸可能在纤连蛋白和具有该序列的其他蛋白质中的细胞附着活性的表达中起作用。这种识别机制可能是许多生物系统所共有的。
A tetrapeptide sequence, Arg-Gly-Asp-Ser, is the minimal structure recognized by cells in the large, adhesive glycoprotein fibronectin. The structural requirements for this cell recognition site were defined by testing several synthetic variants of the active tetrapeptide sequences. The conservative substitutions of lysine for arginine, alanine for glycine, or glutamic acid for aspartic acid each resulted in abrogation of the [rat] cell attachment-promoting activity characteristic of the natural sequence. In the position of the serine residue, some alterations were compatible with activity. Assay of peptides containing the structure Arg-Gly-Asp-X (where X = another amino acid residue) showed that an Arg-Gly-Asp-Val sequence predicted to be present in some, but not all, fibronectin molecules as a result of alternative RNA splicings could potentially create a 2nd cell attachment site in those fibronectin polypeptide chains carrying that sequence. Other proteins with potentially active Arg-Gly-Asp-X sequences include several proteins that are known to interact with the cell surface. Among these are various types of collagens, thrombin, and discoidin, a slime-mold protein that may be involved in cell aggregation. The arginine, glycine, and aspartic acid residues are absolutely required for the cell recognition, and the surrounding amino acids may play a role in the expression of cell attachment activity in fibronectin and other proteins having this sequence. This recognition mechanism may be common to a number of biological systems.