Leung Juliana, Yueh Andrew, Appah Frank S K, Yuan Bing, de los Santos Kenia, Goff Stephen P
Integrated Program in Cellular, Molecular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
EMBO J. 2006 May 17;25(10):2155-66. doi: 10.1038/sj.emboj.7601097. Epub 2006 Apr 20.
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.
莫洛尼鼠白血病病毒（M-MuLV）的基质蛋白（MA）被发现与IQGAP1相互作用，IQGAP1是细胞骨架的重要调节因子。突变研究确定了MA中对相互作用至关重要的残基，对携带MA突变的病毒进行的测试表明，结合与病毒复制之间存在近乎完美的相关性。复制缺陷型突变体在生命周期的早期和晚期均表现出缺陷。从三个不同的复制缺陷型亲本突变体中分离出四种有活力的第二位点回复病毒，在所有情况下，抑制突变均恢复了与IQGAP1的相互作用。MA与IQGAP1的相互作用在体外和体内都很容易检测到。IQGAP1的C末端片段可有效抑制病毒复制，RNA干扰敲低IQGAP1和2会损害病毒复制。我们认为，IQGAPs将病毒与细胞骨架连接起来，以便在细胞内外运输。
