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Determinants of the Endosomal Localization of Sorting Nexin 1

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Journal Mol Biol Cell
Date 2005 Jan 28
PMID 15673616
Citations 23
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Abstract

The sorting nexin (SNX) family of proteins is characterized by sequence-related phox homology (PX) domains. A minority of PX domains bind with high affinity to phosphatidylinositol 3-phosphate [PI(3)P], whereas the majority of PX domains exhibit low affinity that is insufficient to target them to vesicles. SNX1 is located on endosomes, but its low affinity PX domain fails to localize in vivo. The NMR structure of the PX domain of SNX1 reveals an overall fold that is similar to high-affinity PX domains. However, the phosphatidylinositol (PI) binding pocket of the SNX1 PX domain is incomplete; regions of the pocket that are well defined in high-affinity PX domains are highly mobile in SNX1. Some of this mobility is lost upon binding PI(3)P. The C-terminal domain of SNX1 is a long helical dimer that localizes to vesicles but not to the early endosome antigen-1-containing vesicles where endogenous SNX1 resides. Thus, the obligate dimerization of SNX1 that is driven by the C-terminal domain creates a high-affinity PI binding species that properly targets the holo protein to endosomes.

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References
1.
Peter B, Kent H, Mills I, Vallis Y, Butler P, Evans P . BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science. 2003; 303(5657):495-9. DOI: 10.1126/science.1092586. View

2.
Laskowski R, Rullmannn J, MacArthur M, Kaptein R, Thornton J . AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR. 1996; 8(4):477-86. DOI: 10.1007/BF00228148. View

3.
Gullapalli A, Garrett T, Paing M, Griffin C, Yang Y, Trejo J . A role for sorting nexin 2 in epidermal growth factor receptor down-regulation: evidence for distinct functions of sorting nexin 1 and 2 in protein trafficking. Mol Biol Cell. 2004; 15(5):2143-55. PMC: 404011. DOI: 10.1091/mbc.e03-09-0711. View

4.
Xing Y, Liu D, Zhang R, Joachimiak A, Songyang Z, Xu W . Structural basis of membrane targeting by the Phox homology domain of cytokine-independent survival kinase (CISK-PX). J Biol Chem. 2004; 279(29):30662-9. DOI: 10.1074/jbc.M404107200. View

5.
Otsuki T, Kajigaya S, Ozawa K, Liu J . SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein. Biochem Biophys Res Commun. 1999; 265(3):630-5. DOI: 10.1006/bbrc.1999.1731. View