Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p

Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p
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DOI:
10.1074/jbc.c000307200
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发表时间:
2000-08-18
影响因子:
4.8
通讯作者:
Fass, D
Fass, D
中科院分区:
生物学2区
文献类型:
--
作者:
Paz, Y;Elazar, Z;Fass, D

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GATE-16 蛋白参与高尔基内运输,可与 N-乙基马来酰亚胺敏感融合蛋白和高尔基体 SNARE 结合,GATE-16 的酵母直系同源物是自噬因子 Aut7p,GATE-16 还与 GABA 受体相关蛋白 (GABARAP) 密切相关,GABA 受体相关蛋白 (GABARAP) 已被提出通过介导与细胞骨架的相互作用来聚集神经递质受体,并与光神经元微管相关蛋白复合物的 chain-3 亚基。在这里,我们展示了精细至 1.8 埃分辨率的 GATE-16 晶体结构。 GATE-16 包含一个由两个额外的 N 末端螺旋装饰的泛素折叠,与 GATE-16 具有很强的结构相似性但没有可检测到的序列同源性的蛋白质包括介导不同下游功能的 Ras 效应子,但每个效应子都通过形成伪连续 β 片层与 Ras 相互作用。GATE-16 表面表明它以类似的方式结合其靶标。此外,GATE-16 上的第二个潜在蛋白质-蛋白质相互作用位点可以解释在 GATE-16 家族成员中观察到的接头活性。
The GATE-16 protein participates in intra-Golgi transport and can associate with the N-ethylmaleimide-sensitive fusion protein and with Golgi SNAREs, The yeast ortholog of GATE-16 is the autophagocytosis factor Aut7p, GATE-16 is also closely related to the GABA receptor-associated protein (GABARAP), which has been proposed to cluster neurotransmitter receptors by mediating interaction with the cytoskeleton, and to the light chain-3 subunit of the neuronal microtubule-associated protein complex. Here, we present the crystal structure of GATE-16 refined to 1.8 Angstrom resolution. GATE-16 contains a ubiquitin fold decorated by two additional N-terminal helices, Proteins with strong structural similarity but no detectable sequence homology to GATE-16 include Ras effectors that mediate diverse downstream functions, but each interacts with Ras by forming pseudo-continuous beta-sheets, The GATE-16 surface suggests that it binds its targets in a similar manner. Moreover, a second potential protein-protein interaction site on GATE-16 may explain the adapter activity observed for members of the GATE-16 family.