D-retrovirus morphogenetic switch driven by the targeting signal accessibility to Tctex-1 of dynein.
Despite extensive data demonstrating that immature retroviral particle assembly can take place either at the plasma membrane or at a distinct location within the cytoplasm, targeting of viral precursor proteins to either assembly site still remains poorly understood. Biochemical data presented here suggest that Tctex-1, a light chain of the molecular motor dynein, is involved in the intracellular targeting of Mason-Pfizer monkey virus (M-PMV) polyproteins to the cytoplasmic assembly site. Comparison of the three-dimensional structures of M-PMV wild-type matrix protein (wt MA) with a single amino acid mutant (R55F), which redirects assembly from a cytoplasmic site to the plasma membrane, revealed different mutual orientations of their C- and N-terminal domains. This conformational change buries a putative intracellular targeting motif located between both domains in the hydrophobic pocket of the MA molecule, thereby preventing the interaction with cellular transport mechanisms.
Vlach
Jirí
J
Laboratory of NMR Spectroscopy and Department of Biochemistry and Microbiology and Center of Applied Genomics, Institute of Chemical Technology, Prague, Technická 5, 16628 Prague, Czech Republic.
Lipov
Jan
J
Rumlová
Michaela
M
Veverka
Václav
V
Lang
Jan
J
Srb
Pavel
P
Knejzlík
Zdenek
Z
Pichová
Iva
I
Hunter
Eric
E
Hrabal
Richard
R
Ruml
Tomás
T
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism* / Q000821:virology*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D016093:Mason-Pfizer monkey virus / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000378:metabolism*; D056427:t-Complex Genome Region
D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D004398:Dyneins