GAT (GGA and Tom1) domain responsible for ubiquitin binding and ubiquitination
GAT (GGA and Tom1) domain responsible for ubiquitin binding and ubiquitination
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DOI：
10.1074/jbc.m311702200
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发表时间：
2004-02-20
影响因子：
4.8
通讯作者：
Nakayama, K
中科院分区：
文献类型：
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作者：
Shiba, Y;Katoh, Y;Nakayama, K
GGAs（高尔基定位蛋白，γ -适应蛋白耳域同源性，adp -核糖基化因子（ARF）结合蛋白）是一个单体适应蛋白家族，参与从反式高尔基网络到核内体的膜运输。GGA的GAT （GGA和Tom1）结构域先前已被证明与gtp结合的ARF相互作用，并且对GGA的膜募集至关重要。我们发现GAT结构域的c端子结构域与负责ARF结合的n端GAT子结构域不同，它可以结合泛素。这种结合是由GAT结构域的alpha3螺旋一侧的残基与泛素的Ile-44表面斑块上的残基之间的相互作用介导的。GAT结构域与泛素的结合可以通过gtp结合形式的ARF的存在而增强。此外，GGA本身以依赖于gat -泛素相互作用的方式泛素化。这些结果描述了泛素与GAT相互作用的分子基础，并表明gga介导的转运受到泛素系统的调控，就像其他泛素结合蛋白介导的内体转运一样。
GGAs (Golgi-localizing, gamma-adaptin ear domain homology, ADP-ribosylation factor (ARF)-binding proteins) are a family of monomeric adaptor proteins involved in membrane trafficking from the trans-Golgi network to endosomes. The GAT (GGA and Tom1) domains of GGAs have previously been shown to interact with GTP-bound ARF and to be crucial for membrane recruitment of GGAs. Here we show that the C-terminal subdomain of the GAT domain, which is distinct from the N-terminal GAT subdomain responsible for ARF binding, can bind ubiquitin. The binding is mediated by interactions between residues on one side of the alpha3 helix of the GAT domain and those on the so-called Ile-44 surface patch of ubiquitin. The binding of the GAT domain to ubiquitin can be enhanced by the presence of a GTP-bound form of ARF. Furthermore, GGA itself is ubiquitinated in a manner dependent on the GAT-ubiquitin interaction. These results delineate the molecular basis for the interaction between ubiquitin and GAT and suggest that GGA-mediated trafficking is regulated by the ubiquitin system as endosomal trafficking mediated by other ubiquitin-binding proteins.