Recruitment of TIP47 to lipid droplets is controlled by the putative hydrophobic cleft
Recruitment of TIP47 to lipid droplets is controlled by the putative hydrophobic cleft
复制标题
DOI：
10.1016/j.bbrc.2006.06.074
复制
发表时间：
2006-08-18
影响因子：
3.1
通讯作者：
Fujimoto, Toyoshi
中科院分区：
文献类型：
--
作者：
Ohsaki, Yuki;Maeda, Takashi;Fujimoto, Toyoshi
脂肪分化相关蛋白 (ADRP) 和 TIP47 显示出序列相似性，特别是在它们的 N 末端 PAT-1 结构域中。在标准培养条件下，ADRP 存在于大多数脂滴 (LD) 中，而 TIP47 仅在某些 LD 中观察到，并在脂肪酸处理后被招募到 LD 中。通过分析缺失突变体，我们发现 TIP47 的 C 端一半，或更具体地说是假定的疏水性裂口 [S.J.希肯伯顿，A.R. Kimmel, C. 隆多斯, J.H. Hurley，《PAT 家族成员 TIP47 脂滴蛋白的结构》，Structure (Camb) 12 (2004) 1199-1207.]，参与 LD 靶向和对脂肪酸的反应。该结果与 ADRP 观察到的结果形成对比，暗示 TIP47 具有独特的 LD 靶向机制。与此一致的是，Rab18 的过表达降低了 LD 中的 ADRP，但不降低 TIP47，并且 TIP47 没有取代 LD 中预先存在的 ADRP。但 ADRP 可能是控制 TIP47 行为的一个因素，因为 LD 中的 TIP47 在 ADRP 下调时增加。结果表明，假定的疏水性裂缝对于 TIP47 的独特特性至关重要。 (c) 2006 Elsevier Inc. 保留所有权利。
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. (c) 2006 Elsevier Inc. All rights reserved.