A Neural-specific F-box Protein Fbs1 Functions as a Chaperone Suppressing Glycoprotein Aggregation*
A Neural-specific F-box Protein Fbs1 Functions as a Chaperone Suppressing Glycoprotein Aggregation*
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DOI：
10.1074/jbc.m611168200
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发表时间：
2007-03
影响因子：
4.8
通讯作者：
Y. Yoshida;Arisa Murakami;K. Iwai;Keiji Tanaka
中科院分区：
文献类型：
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作者：
Y. Yoshida;Arisa Murakami;K. Iwai;Keiji Tanaka
Fbs1是一种广泛存在于神经系统中的F-box蛋白。与普遍表达的Fbs2类似，Fbs1识别最内侧的N-糖链是未折叠糖蛋白的信号，可能是在内质网相关的降解途径中。在这里，我们证明了在体内大多数Fbs1以Fbs1-Skp1异二聚体或Fbs1单体存在，而不是SCFFbs1复合体。Fbs1的低效率SCF复合体的形成和SCFFbs1结合在内质网膜上的限制是由于F-box结构域和糖结合结构域之间的短连接序列所致。在体外，Fbs1通过Fbs1的N末端唯一序列阻止糖蛋白的聚集。我们的结果表明，Fbs1通过抑制聚集体的形成来帮助清除神经细胞中的异常糖蛋白，这与泛素连接酶的活性无关，因此Fbs1是这些蛋白的独特伴侣。
Fbs1 is an F-box protein present abundantly in the nervous system. Similar to the ubiquitously expressed Fbs2, Fbs1 recognizes N-glycans at the innermost position as a signal for unfolded glycoproteins, probably in the endoplasmic reticulum-associated degradation pathway. Here, we show that the in vivo majority of Fbs1 is present as Fbs1-Skp1 heterodimers or Fbs1 monomers but not SCFFbs1 complex. The inefficient SCF complex formation of Fbs1 and the restricted presence of SCFFbs1 bound on the endoplasmic reticulum membrane were due to the short linker sequence between the F-box domain and the sugar-binding domain. In vitro, Fbs1 prevented the aggregation of the glycoprotein through the N-terminal unique sequence of Fbs1. Our results suggest that Fbs1 assists clearance of aberrant glycoproteins in neuronal cells by suppressing aggregates formation, independent of ubiquitin ligase activity, and thus functions as a unique chaperone for those proteins.