Stanley Will A, Filipp Fabian V, Kursula Petri, Schüller Nicole, Erdmann Ralf, Schliebs Wolfgang, Sattler Michael, Wilmanns Matthias
European Molecular Biology Laboratory-Hamburg Outstation, Notkestrasse 85, 22603 Hamburg.
Structural and Computational Biology Unit, European Molecular Biology Laboratory-Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg.
Mol Cell. 2006 Dec 8;24(5):653-663. doi: 10.1016/j.molcel.2006.10.024.
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.
过氧化物酶体需要将各种大小的折叠且具有功能的靶蛋白转运过过氧化物酶体膜。我们研究了主要导入受体Pex5p的结构和功能，该受体识别带有C端1型过氧化物酶体靶向信号的靶标。在存在和不存在过氧化物酶体靶标、固醇载体蛋白2的情况下，该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倍四肽重复序列片段C端的一个长环引起的。该环残基的突变导致人类成纤维细胞过氧化物酶体导入缺陷。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，使货物能够保留其天然结构和功能。
