Interaction of Moloney murine leukemia virus matrix protein with IQGAP.
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.
Leung
Juliana
J
Integrated Program in Cellular, Molecular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Yueh
Andrew
A
Appah
Frank S K
FS
Yuan
Bing
B
de los Santos
Kenia
K
Goff
Stephen P
SP
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; D020703:ras GTPase-Activating Proteins