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Structure of the PX domain of SNX 25 reveals a novel phospholipid recognition model by dimerization in the PX domain
Author(s) -
Su Kai,
Xu Tingting,
Yu Zhijun,
Zhu Jiabin,
Zhang Yulong,
Wu Minhao,
Xiong Ying,
Liu Jinsong,
Xu Jinxin
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12688
Subject(s) - endosome , microbiology and biotechnology , chemistry , sorting nexin , c2 domain , domain (mathematical analysis) , receptor , biology , biochemistry , membrane , mathematical analysis , mathematics
SNX 25, a regulator of GPCR signaling‐phox‐homology ( PX ) domain containing sorting nexin ( SNX ) member, has been proposed to be involved in the lysosomal degradation of the transforming growth factor β receptor and the development of temporal lobe epilepsy. Targeting to the endosomal membranes by the specific binding of phosphorylated phosphatidylinositols (PIPs) through the PX domain is critical for the function of SNX s. However, the mechanism for SNX 25‐ PX targeting to the endosomes remains unclear. Here, we demonstrate that the PX domain of zebrafish SNX 25 ( zSNX 25‐ PX ) is capable of binding to PI 3P only in its dimeric form. We also present the crystal structure of zSNX 25‐ PX . Combined with biochemical experiments, we further identify a potential PI 3P‐binding region and propose a novel PI ‐binding model based on dimerization in the PX domain of SNX s.