Kim Il Hwan, Pham Van, Jablonka Willy, Goodman Walter G, Ribeiro José M C, Andersen John F
From the Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
the Department of Entomology, University of Wisconsin-Madison, Madison, Wisconsin 53706.
J Biol Chem. 2017 Sep 15;292(37):15329-15339. doi: 10.1074/jbc.M117.802009. Epub 2017 Jul 27.
Juvenile hormone (JH) is a key regulator of insect development and reproduction. In adult mosquitoes, it is essential for maturation of the ovary and normal male reproductive behavior, but how JH distribution and activity is regulated after secretion is unclear. Here, we report a new type of specific JH-binding protein, given the name mosquito juvenile hormone-binding protein (mJHBP), which circulates in the hemolymph of pupal and adult males and females. mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are present in the genomes of , , and mosquito species. Using isothermal titration calorimetry, we show that mJHBP specifically binds JH II and JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the presence of JH III and found to have a double OBP domain structure reminiscent of salivary "long" D7 proteins of mosquitoes. We observed that a single JH III molecule is contained in the N-terminal domain binding pocket that is closed in an apparent conformational change by a C-terminal domain-derived α-helix. The electron density for the ligand indicated a high occupancy of the natural 10 enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP from lepidopteran insects. A low level of expression of mJHBP in larvae suggests that it is primarily active during the adult stage where it could potentially influence the effects of JH on egg development, mating behavior, feeding, or other processes.
保幼激素(JH)是昆虫发育和繁殖的关键调节因子。在成年蚊子中,它对卵巢成熟和正常的雄性生殖行为至关重要,但分泌后保幼激素的分布和活性是如何调节的尚不清楚。在此,我们报道了一种新型的特异性保幼激素结合蛋白,命名为蚊子保幼激素结合蛋白(mJHBP),它在蛹期和成年雌雄蚊子的血淋巴中循环。mJHBP是气味结合蛋白(OBP)家族的成员,在、和蚊子物种的基因组中存在直系同源物。使用等温滴定量热法,我们表明mJHBP特异性结合JH II和JH III,但不结合类二十烷酸或JH衍生物。mJHBP在JH III存在的情况下结晶,发现具有双OBP结构域结构,让人联想到蚊子唾液中的“长”D7蛋白。我们观察到,一个JH III分子包含在N端结构域结合口袋中,该口袋通过C端结构域衍生的α螺旋以明显的构象变化关闭。配体的电子密度表明JH III的天然10对映体具有高占有率。值得注意的是,mJHBP在结构上与鳞翅目昆虫的血淋巴JHBP无关。mJHBP在幼虫中的低水平表达表明它主要在成年阶段活跃,在该阶段它可能会影响保幼激素对卵子发育、交配行为、进食或其他过程的作用。