Vlach Jirí, Lipov Jan, Rumlová Michaela, Veverka Václav, Lang Jan, Srb Pavel, Knejzlík Zdenek, Pichová Iva, Hunter Eric, Hrabal Richard, Ruml Tomás
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.
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10565-70. doi: 10.1073/pnas.0801765105. Epub 2008 Jul 22.
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.
尽管有大量数据表明未成熟的逆转录病毒颗粒组装可发生在质膜或细胞质内的特定位置，但病毒前体蛋白靶向这两个组装位点的机制仍知之甚少。本文提供的生化数据表明，分子马达动力蛋白的轻链Tctex-1参与了梅森- Pfizer猴病毒（M-PMV）多蛋白向细胞质组装位点的细胞内靶向运输。将M-PMV野生型基质蛋白（wt MA）与单个氨基酸突变体（R55F）的三维结构进行比较，后者将组装位点从细胞质位点重新定向到质膜，结果显示它们的C端和N端结构域具有不同的相互取向。这种构象变化将位于两个结构域之间的一个假定的细胞内靶向基序埋入MA分子的疏水口袋中，从而阻止了与细胞运输机制的相互作用。
