Recognition of a functional peroxisome type 1 target by the dynamic import receptor Pex5p
Recognition of a functional peroxisome type 1 target by the dynamic import receptor Pex5p
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DOI：
10.1016/j.molcel.2006.10.024
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发表时间：
2006-12-08
期刊：
影响因子：
16
通讯作者：
Wilmanns, Matthias
中科院分区：
文献类型：
--
作者：
Stanley, Will A.;Filipp, Fabian V.;Wilmanns, Matthias
过氧化物酶体需要不同大小的折叠和功能靶蛋白在过氧化物酶体膜上进行易位。我们研究了主要输入受体Pex5p的结构和功能，该受体识别带有c端过氧化物酶体靶向信号类型1的靶标。在存在和不存在过氧化物酶体靶点（固醇载体蛋白2）的情况下，受体的晶体结构揭示了从开放的蜗牛状构象到封闭的圆形构象的主要结构变化。这些变化是由7倍四肽重复片段的长环C末端引起的。该环残基的突变导致人成纤维细胞过氧化物酶体输入缺陷。受体/货物复合物的结构表明，货物的主要受体结合位点在结构和拓扑上是自主的，使货物保持其原有的结构和功能。
Peroxisomes require the translocation of folded and functional target proteins of various sizes across the peroxisomal membrane. We have investigated the structure and function of the principal import receptor Pex5p, which recognizes targets bearing a C-terminal peroxisomal targeting signal type 1. Crystal structures of the receptor in the presence and absence of a peroxisomal target, sterol carrier protein 2, reveal major structural changes from an open, snail-like conformation into a closed, circular conformation. These changes are caused by a long loop C terminal to the 7-fold tetratricopeptide repeat segments. Mutations in residues of this loop lead to defects in peroxisomal import in human fibroblasts. The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function.