Leukemogenic membrane glycoprotein encoded by Friend spleen focus-forming virus: transport to cell surfaces and shedding are controlled by disulfide-bonded dimerization and by cleavage of a hydrophobic membrane anchor.
Leukemogenic membrane glycoprotein encoded by Friend spleen focus-forming virus: transport to cell surfaces and shedding are controlled by disulfide-bonded dimerization and by cleavage of a hydrophobic membrane anchor.
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由 Friend 脾病灶形成病毒编码的致白血病膜糖蛋白：运输到细胞表面和脱落由二硫键二聚化和疏水膜锚的裂解控制。
DOI：
10.1128/jvi.63.9.3561-3568.1989
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发表时间：
1989
影响因子：
5.4
通讯作者：
Kabat,D
中科院分区：
文献类型：
--
作者：
Gliniak,BC;Kabat,D
Friend 脾病灶形成病毒编码的致白血病糖蛋白 (gp55) 主要保留在粗面内质网 (RER) 中。然而，一小部分（约 5%）被加工形成衍生物，出现在质膜上并导致受感染的成红细胞有丝分裂。我们现在发现 gp55 在 RER 中异质折叠，形成具有不同二硫键的成分，这种差异可能决定它们的加工命运。 RER gp55 主要由具有链内二硫键的单体组成。相反，加工后的分子是二硫键二聚体。通过将四种 N-连接高甘露糖寡糖转化为复杂衍生物以及通过附着唾液酸化 O-连接寡糖，这些二聚体在转运到细胞表面的过程中被广泛修饰。然后质膜二聚体通过一种机制缓慢地脱落到培养基中，该机制涉及从糖蛋白的羧基末端蛋白水解裂解大约25个膜锚定疏水性氨基酸。因此，脱落分子的多肽链比细胞相关的 gp55 短。我们得出结论，gp55 折叠成不同的二硫键组分，这些组分基本上不异构化，并且只有一种特定的二聚体能够从 RER 输出。 gp55 的有丝分裂活性可能是由细胞表面二聚体、脱落衍生物或脱落反应后保留在膜中的羧基末端疏水锚引起的。
The leukemogenic glycoprotein (gp55) encoded by Friend spleen focus-forming virus is predominantly retained in the rough endoplasmic reticulum (RER). However, a small proportion (ca. 5%) is processed to form a derivative that occurs on plasma membranes and causes mitosis of infected erythroblasts. We have now found that gp55 folds heterogeneously in the RER to form components with different disulfide bonds and that this difference may determine their processing fates. RER gp55 consists predominantly of monomers with intrachain disulfide bonds. In contrast, the processed molecules are disulfide-bonded dimers. These dimers are extensively modified in transit to cell surfaces by conversion of four N-linked high-mannose oligosaccharides to complex derivatives and by attachment of a sialylated O-linked oligosaccharide. The plasma membrane dimers are then slowly shed into the medium by a mechanism that involves proteolytic cleavage of approximately 25 membrane-anchoring hydrophobic amino acids from the carboxyl termini of the glycoproteins. Consequently, shed molecules have shorter polypeptide chains than cell-associated gp55. We conclude that gp55 folds into different disulfide-bonded components that do not substantially isomerize, and that only one specific dimer is competent for export from the RER. Mitogenic activity of gp55 could be caused by the cell surface dimers, by the shed derivative, or by the carboxyl-terminal hydrophobic anchors that remain in the membranes after the shedding reaction.