Interaction of Moloney murine leukemia virus matrix protein with IQGAP
Interaction of Moloney murine leukemia virus matrix protein with IQGAP
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DOI：
10.1038/sj.emboj.7601097
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发表时间：
2006-05-17
期刊：
影响因子：
11.4
通讯作者：
Goff, Stephen P.
中科院分区：
文献类型：
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作者：
Leung, Juliana;Yueh, Andrew;Goff, Stephen P.
莫洛尼鼠白血病病毒（M-MuLV）的基质蛋白（MA）被发现与IQGAP 1相互作用，IQGAP 1是细胞骨架的重要调节因子。突变研究确定了MA的相互作用的关键残基，携带MA突变的病毒的测试显示了结合和病毒复制之间近乎完美的相关性。复制缺陷型突变体在生命周期的早期和晚期都表现出缺陷。从三种不同的复制缺陷型亲本突变体中分离出四种可行的第二位点回复突变病毒，在所有情况下，通过抑制突变恢复了与IQGAP 1的相互作用。MA和IQGAP 1的相互作用很容易在体外和体内检测到。病毒复制被IQGAP 1的C-末端片段有力地抑制，并且被IQGAP 1和2的RNAi敲低所损害。我们认为IQGAP将病毒连接到细胞骨架上，以便运输到细胞内外。
The matrix protein ( MA) of the Moloney murine leukemia virus (M-MuLV) was found to interact with IQGAP1, a prominent regulator of the cytoskeleton. Mutational studies defined residues of MA critical for the interaction, and tests of viruses carrying MA mutations revealed a near-perfect correlation between binding and virus replication. The replication-defective mutants showed defects in both early and late stages of the life cycle. Four viable second-site revertant viruses were isolated from three different replication-defective parental mutants, and in all cases the interaction with IQGAP1 was restored by the suppressor mutations. The interaction of MA and IQGAP1 was readily detected in vitro and in vivo. Virus replication was potently inhibited by a C-terminal fragment of IQGAP1, and impaired by RNAi knockdown of IQGAP1 and 2. We suggest that the IQGAPs link the virus to the cytoskeleton for trafficking both into and out of the cell.