Proteolytic Activation of Respiratory Syncytial Virus Fusion Protein
Proteolytic Activation of Respiratory Syncytial Virus Fusion Protein
复制标题
呼吸道合胞病毒融合蛋白的蛋白水解激活
DOI：
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发表时间：
2001
影响因子：
4.8
通讯作者：
G. Herrler
中科院分区：
文献类型：
--
作者：
G. Zimmer;Linda Budz;G. Herrler
呼吸道合胞病毒的F（融合）蛋白被合成为无活性前体F0，其在多碱基序列KKRKRR 136处被细胞蛋白酶弗林蛋白酶蛋白水解加工成亚基F1和F2。该成熟过程对于F蛋白获得融合能力是必不可少的。我们观察到，蛋白水解裂解另外发生在另一个基本基序，RARR 109，也满足弗林蛋白酶识别的要求。在两个位点的切割导致从多肽链上除去27个氨基酸的糖基化肽。当通过定点诱变将序列RARR 109改变为NANR 109或RANN 109时，完全阻止了弗林蛋白酶的切割。虽然突变体仍然在Arg136位被加工，但它们没有显示任何合胞体形成。通过用胰蛋白酶处理转染的细胞，将F突变体转化成其融合形式，实现了修饰的基序的蛋白水解切割。我们的研究结果表明，这两个弗林蛋白酶的共识序列被切割，以激活融合蛋白。
The F (fusion) protein of the respiratory syncytial viruses is synthesized as an inactive precursor F0 that is proteolytically processed at the multibasic sequence KKRKRR136 into the subunits F1 and F2 by the cellular protease furin. This maturation process is essential for the F protein to gain fusion competence. We observed that proteolytic cleavage additionally occurs at another basic motif, RARR109 , that also meets the requirements for furin recognition. Cleavage at both sites leads to the removal from the polypeptide chain of a glycosylated peptide of 27 amino acids. When the sequence RARR109 was changed to NANR109 or to RANN109 by site-directed mutagenesis, cleavage by furin was completely prevented. Although the mutants were still processed at position Arg136, they did not show any syncytia formation. Proteolytic cleavage of the modified motifs was achieved by treatment of transfected cells with trypsin converting the F mutants into their fusogenic forms. Our findings indicate that both furin consensus sequences have to be cleaved in order to activate the fusion protein.
影响因子：
3.7
作者：
KAWAOKA, Y;NAEVE, CW;WEBSTER, RG
通讯作者：
WEBSTER, RG
影响因子：
3.7
作者：
Hallak, LK;Collins, PL;Peeples, ME
通讯作者：
Peeples, ME
DOI：
10.1073/pnas.86.23.9313
发表时间：
1989-12
影响因子：
11.1
作者：
A. Bivic;Francisco X. REALt;Enrique;RODRIGUEZ-BOULAN
通讯作者：
A. Bivic;Francisco X. REALt;Enrique;RODRIGUEZ-BOULAN