Ohsaki Yuki, Maeda Takashi, Maeda Mari, Tauchi-Sato Kumi, Fujimoto Toyoshi
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Japan.
Biochem Biophys Res Commun. 2006 Aug 18;347(1):279-87. doi: 10.1016/j.bbrc.2006.06.074. Epub 2006 Jun 21.
Adipose differentiation-related protein (ADRP) and TIP47 show sequence similarity, particularly in their N-terminal PAT-1 domain. Under standard culture conditions, ADRP existed in most lipid droplets (LDs), whereas TIP47 was observed only in some LDs and recruited to LDs on treatment with fatty acids. By analyzing deletion mutants, we found that the C-terminal half of TIP47, or more specifically the putative hydrophobic cleft [S.J. Hickenbottom, A.R. Kimmel, C. Londos, J.H. Hurley, Structure of a lipid droplet protein; the PAT family member TIP47, Structure (Camb) 12 (2004) 1199-1207.], was involved in LD targeting and responsiveness to fatty acids. The result contrasted with that observed for ADRP and implied a distinct LD-targeting mechanism for TIP47. Consistent with this, overexpression of Rab18 decreased ADRP, but not TIP47, from LDs, and TIP47 did not displace pre-existing ADRP from LDs. But ADRP may be a factor to control the TIP47 behavior, because TIP47 in LDs increased upon down-regulation of ADRP. The results suggested that the putative hydrophobic cleft is critical for the unique characteristics of TIP47.
脂肪分化相关蛋白（ADRP）与TIP47在序列上具有相似性，尤其是在它们的N端PAT-1结构域。在标准培养条件下，ADRP存在于大多数脂滴（LDs）中，而TIP47仅在一些脂滴中被观察到，并且在脂肪酸处理后被募集到脂滴上。通过分析缺失突变体，我们发现TIP47的C端一半，或者更具体地说是推测的疏水裂缝[S.J. Hickenbottom, A.R. Kimmel, C. Londos, J.H. Hurley, 脂滴蛋白的结构；PAT家族成员TIP47，《结构（坎布里奇）》12（2004）1199 - 1207。]，参与了脂滴靶向以及对脂肪酸的反应。该结果与ADRP的情况形成对比，这暗示了TIP47有独特的脂滴靶向机制。与此一致的是，Rab18的过表达使脂滴中的ADRP减少，但不影响TIP47，并且TIP47不会取代脂滴中预先存在的ADRP。但是ADRP可能是控制TIP47行为的一个因素，因为在ADRP下调后，脂滴中的TIP47增加。这些结果表明，推测的疏水裂缝对于TIP47的独特特性至关重要。
