Cellular transformation by a transmembrane peptide: structural requirements for the bovine papillomavirus E5 oncoprotein.
Cellular transformation by a transmembrane peptide: structural requirements for the bovine papillomavirus E5 oncoprotein.
复制标题
跨膜肽的细胞转化：牛乳头瘤病毒 E5 癌蛋白的结构要求。
DOI：
10.1073/pnas.91.11.4634
复制
发表时间：
1994
影响因子：
11.1
通讯作者：
Donoghue,DJ
中科院分区：
文献类型：
--
作者：
Meyer,AN;Xu,YF;Webster,MK;Smith,AE;Donoghue,DJ
牛乳头瘤病毒的E5癌蛋白只有44个氨基酸，以二硫键跨膜二聚体的形式存在。这种重要的癌蛋白通过激活血小板衍生生长因子(PDGF)受体来刺激信号转导，而E5与PDGF的氨基酸序列相似。结果表明，疏水性跨膜区的一个关键特征是参与螺旋间氢键形成的氨基酸侧链。这些数据让人想起激活的neu癌基因，在该基因中，跨膜区域的点突变导致配体无关的二聚化和受体酪氨酸激酶的激活。值得注意的是，E5的跨膜区可以被激活的neu受体酪氨酸激酶的跨膜区所取代。广泛的突变定义了E5癌蛋白转化所需的最低结构特征，第一，二聚的能力，第二，在膜的胞外侧呈现带负电荷的残基。缺乏与PDGF相似的大部分氨基酸残基的E5突变体的生物学活性表明，E5和PDGF通过不同的机制激活PDGF受体。
The E5 oncoprotein of bovine papillomavirus, only 44 amino acids long, occurs as a disulfide-bonded transmembrane dimer. This remarkable oncoprotein stimulates signal transduction through activation of the platelet-derived growth factor (PDGF) receptor, and E5 exhibits limited amino acid sequence similarity with PDGF. Results presented here suggest that a key feature of the hydrophobic transmembrane domain is an amino acid side chain that participates in interhelical hydrogen bond formation. These data are reminiscent of the activated neu oncogene, in which a point mutation in the transmembrane domain leads to ligand-independent dimerization and activation of a receptor tyrosine kinase. Significantly, the transmembrane domain of E5 can be largely replaced by the transmembrane domain from the activated neu receptor tyrosine kinase. Extensive mutagenesis defines the minimal structural features required for transformation by the E5 oncoprotein as, first, the ability to dimerize and, second, presentation of a negatively charged residue at the extracellular side of the membrane. The biological activity of E5 mutants that lack most amino acid residues similar to PDGF suggests that E5 and PDGF activate the PDGF receptor by distinct mechanisms.