Horiguchi Yuka, Araki Makoto, Motojima Kiyoto
Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Arch Biochem Biophys. 2008 Nov 15;479(2):121-30. doi: 10.1016/j.abb.2008.08.020. Epub 2008 Sep 10.
17beta-Hydroxysteroid dehydrogenase type 11 (17betaHSD11) is mostly localized on the endoplasmic reticulum (ER) membrane under normal conditions and redistributes to lipid droplets (LDs) when the formation of LDs is induced. In this study, confocal microscopy analyses of the subcellular localization of the mutated 17betaHSD11 proteins in cells with or without LDs revealed that both an N-terminal hydrophobic sequence and an adjacent sequence that has a weak homology with the PAT motif are independently necessary and both parts together (28 amino acid residues in total) are sufficient for the dual localization of 17betaHSD11. Mutation analyses suggest that the PAT-like motif in 17betaHSD11 will not be functionally similar to the canonical PAT motif. Hsp60 was identified as a possibly interacting protein with the PAT-like motif, and biochemical and microscopic analyses suggest that Hsp60 may be partly, but not necessarily involved in recognition of the PAT-like part of the targeting sequence of 17betaHSD11.
17β-羟类固醇脱氢酶11型（17βHSD11）在正常条件下主要定位于内质网（ER）膜上，当脂质滴（LDs）形成被诱导时会重新分布到脂质滴上。在本研究中，对有或无脂质滴的细胞中突变的17βHSD11蛋白的亚细胞定位进行共聚焦显微镜分析发现，N端疏水序列和与PAT基序有弱同源性的相邻序列各自都是必需的，且这两部分共同作用（总共28个氨基酸残基）对于17βHSD11的双重定位是足够的。突变分析表明，17βHSD11中的PAT样基序在功能上与典型的PAT基序不同。热休克蛋白60（Hsp60）被鉴定为可能与PAT样基序相互作用的蛋白，生化和显微镜分析表明，Hsp60可能部分但不一定参与识别17βHSD11靶向序列的PAT样部分。
