Crystal structure of the human GGA1 GAT domain.
Crystal structure of the human GGA1 GAT domain.
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人类 GGA1 GAT 结构域的晶体结构。
DOI：
10.1021/bi034334n
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Zhang,XuejunC
中科院分区：
文献类型：
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作者：
Zhu,Guangyu;Zhai,Peng;He,Xiangyuan;Terzyan,Simon;Zhang,Rongguang;Joachimiak,Andrzej;Tang,Jordan;Zhang,XuejunC
gga是一个在细胞内蛋白质运输中起作用的囊泡包覆调节蛋白家族。GGA分子包含四个结构域，每个结构域在进行细胞内运输时介导与其他蛋白质的相互作用。GGAs的GAT结构域已被确定为结合膜结合ARF的结构实体，ARF是调节囊泡-包被组装的分子开关。它还直接与rabaptin5相互作用，rabaptin5是核内体融合的重要组成部分。本文报道了人类GGA1 GAT结构域的2.8 Å分辨率晶体结构。GAT结构域包含四个螺旋，形状拉长，最长尺寸超过80 Å。其最长的螺旋涉及两个结构基序：一个n端螺旋-环-螺旋基序和一个c端三螺旋束。n端基序包含GGA - GAT结构域中最保守的氨基酸序列。在这个保守区域内，先前与ARF结合有关的残基簇形成疏水表面斑块，这可能是ARF的结合位点。此外，基于结构的诱变-生化分析表明，GAT结构域的c端三螺旋束负责rabaptin5的结合。这些结构特征与支持GAT领域多个功能角色的模型是一致的。
GGAs are a family of vesicle-coating regulatory proteins that function in intracellular protein transport. A GGA molecule contains four domains, each mediating interaction with other proteins in carrying out intracellular transport. The GAT domain of GGAs has been identified as the structural entity that binds membrane-bound ARF, a molecular switch regulating vesicle−coat assembly. It also directly interacts with rabaptin5, an essential component of endosome fusion. A 2.8 Å resolution crystal structure of the human GGA1 GAT domain is reported here. The GAT domain contains four helices and has an elongated shape with the longest dimension exceeding 80 Å. Its longest helix is involved in two structural motifs: an N-terminal helix−loop−helix motif and a C-terminal three-helix bundle. The N-terminal motif harbors the most conservative amino acid sequence in the GGA GAT domains. Within this conserved region, a cluster of residues previously implicated in ARF binding forms a hydrophobic surface patch, which is likely to be the ARF-binding site. In addition, a structure-based mutagenesis−biochemical analysis demonstrates that the C-terminal three-helix bundle of this GAT domain is responsible for the rabaptin5 binding. These structural characteristics are consistent with a model supporting multiple functional roles for the GAT domain.