Structural basis for recognition of acidic-cluster dileucine sequence by GGA1
Structural basis for recognition of acidic-cluster dileucine sequence by GGA1
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DOI：
10.1038/415937a
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发表时间：
2002-02-21
期刊：
影响因子：
64.8
通讯作者：
Wakatsuki, S
中科院分区：
文献类型：
--
作者：
Shiba, T;Takatsu, H;Wakatsuki, S
GGA（Golgi定位、g-适应蛋白耳部同源结构域、ARF相互作用蛋白）对于通过与TGN分选受体、ADP-核糖基化因子（ARF）和网格蛋白（1，2）的相互作用将可溶性蛋白从反式高尔基网络（TGN）转运到内体/溶酶体至关重要。GGA的氨基末端VHS结构域通过识别酸性簇双亮氨酸（ACLL）序列与分选受体的胞质结构域形成复合物（1-6）。在这里，我们报告的X-射线结构的GGA 1 VHS域单独，并在复杂的阳离子非依赖性甘露糖6-磷酸受体的羧基末端肽含有ACLL序列。VHS结构域形成具有八个α-螺旋的超螺旋，类似于TOM 1和Hrs的VHS结构域。螺旋α 6和α 8以及它们的一些侧链的单向运动产生了一组静电和疏水相互作用，用于正确识别ACLL肽。这种识别机制为调节蛋白质从TGN转运到内体/溶酶体提供了基础，这是分拣蛋白和低密度脂蛋白受体相关蛋白所共有的。
GGAs (Golgi-localizing, g-adaptin ear homology domain, ARF-interacting proteins) are critical for the transport of soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes by means of interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF), and clathrin(1,2). The amino-terminal VHS domains of GGAs form complexes with the cytoplasmic domains of sorting receptors by recognizing acidic-cluster dileucine (ACLL) sequences(1-6). Here we report the X-ray structure of the GGA1 VHS domain alone, and in complex with the carboxyterminal peptide of cation-independent mannose 6-phosphate receptor containing an ACLL sequence. The VHS domain forms a super helix with eight alpha-helices, similar to the VHS domains of TOM1 and Hrs. Unidirectional movements of helices alpha6 and alpha8, and some of their side chains, create a set of electrostatic and hydrophobic interactions for correct recognition of the ACLL peptide. This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein.