Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Structure. 2018 Oct 2;26(10):1373-1383.e4. doi: 10.1016/j.str.2018.07.009. Epub 2018 Aug 30.
Melanoregulin (Mreg) is a small, highly charged, multiply palmitoylated protein present on the membrane of melanosomes. Mreg is implicated in the transfer of melanosomes from melanocytes to keratinocytes, and in promoting the microtubule minus end-directed transport of these organelles. The possible molecular function of Mreg was identified by solving its structure using nuclear magnetic resonance (NMR) spectroscopy. Mreg contains six α helices forming a fishhook-like fold in which positive and negative charges occupy opposite sides of the protein's surface and sandwich a putative, cholesterol recognition sequence (CRAC motif). Mreg containing a point mutation within its CRAC motif still targets to late endosomes/lysosomes, but no longer promotes their microtubule minus end-directed transport. Moreover, wild-type Mreg does not promote the microtubule minus end-directed transport of late endosomes/lysosomes in cells transiently depleted of cholesterol. Finally, reversing the charge of three clustered acidic residues partially inhibits Mreg's ability to drive these organelles to microtubule minus ends.
黑素皮质素（Mreg）是一种带正电荷的、高度带电荷的、多棕榈酰化的蛋白质，存在于黑素小体的膜上。Mreg 参与黑素小体从黑素细胞向角质细胞的转移，并促进这些细胞器的微管负端定向运输。通过核磁共振（NMR）光谱法解决其结构，确定了 Mreg 的可能分子功能。Mreg 包含六个α螺旋，形成一个鱼钩状折叠，其中正电荷和负电荷占据蛋白质表面的相对侧，并夹在一个假定的胆固醇识别序列（CRAC 基序）上。CRAC 基序内发生点突变的 Mreg 仍靶向晚期内体/溶酶体，但不再促进它们的微管负端定向运输。此外，野生型 Mreg 不会促进胆固醇瞬时耗尽的细胞中晚期内体/溶酶体的微管负端定向运输。最后，反转三个聚集酸性残基的电荷会部分抑制 Mreg 将这些细胞器驱动到微管负端的能力。
