DETERMINANTS OF SUBSTRATE RECOGNITION BY POLIOVIRUS-2A PROTEINASE

被引:62
作者
HELLEN, CUT
LEE, CK
WIMMER, E
机构
关键词
D O I
10.1128/JVI.66.6.3330-3338.1992
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Poliovirus proteinase 2A (2A(pro)) is autocatalytically released from the viral polyprotein by cleavage in cis of a Tyr-Gly dipeptide at its own amino terminus, resulting in separation of the P1 structural and P2-P3 nonstructural protein precursors. A second Ty-Gly dipeptide within 3D polymerase is cleaved by 2A(pro) in trans, but this is not essential for viral proliferation. The mechanism which limits cleavage to only 2 of the 10 Tyr-Gly dipeptides within the poliovirus polyprotein has not been characterized. We have therefore undertaken a systematic mutational analysis of the VP1-2A site to elucidate determinants of substrate recognition by 2A(pro). The P2 and P1' positions are important determinants for cis cleavage of this site, whereas a variety of substituents could be tolerated at the P2', P1, and P3 positions. The requirements for trans cleavage of this site were more stringent. We found that the 2A(pro) of coxsackievirus type A21 and rhinoviruses 2 and 14 have stringent requirements similar to those of poliovirus 2A(pro) for cleavage in trans.
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页码:3330 / 3338
页数:9
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