Abstract
Sorting nexins are phox homology (PX) domain-containing proteins involved in diverse intracellular endosomal trafficking pathways. The PX domain binds to certain phosphatidylinositols and is recruited to vesicles rich in these lipids. The structure of the PX domain is highly conserved, containing a three-stranded β-sheet, followed by three α-helices. Here, we report the crystal structures of truncated human SNX11 (sorting nexin 11). The structures reveal that SNX11 contains a novel PX domain, hereby named the extended PX (PXe) domain, with two additional α-helices at the C terminus. We demonstrate that these α-helices are indispensible for the in vitro functions of SNX11. We propose that this PXe domain is present in SNX10 and is responsible for the vacuolation activity of SNX10. Thus, this novel PXe domain constitutes a structurally and functionally important PX domain subfamily.
Highlights
SNX10 and SNX11 exhibit antagonistic activity in regulating endosome vacuolation
Crystal Structure of hSNX11—Two constructs of hSNX11 were generated for the structural study, one with residues 7–142 and the other with residues 7–170. hSNX11-142C crystallized in space group P21 and contains two molecules in the asymmetric unit. hSNX11170C crystallized in space group P212121 and contains one molecule in the asymmetric unit
Both structures contain a conventional phox homology (PX) domain fold composed of a -sheet with three antiparallel -strands, a helical subdomain consisting of three ␣-helices, and a polyproline II (PPII) loop
Summary
SNX10 and SNX11 exhibit antagonistic activity in regulating endosome vacuolation. Results: Two additional ␣-helices downstream of the conventional PX domain were identified in the SNX11 crystal structure. Sorting nexins are phox homology (PX) domain-containing proteins involved in diverse intracellular endosomal trafficking pathways. The structures reveal that SNX11 contains a novel PX domain, hereby named the extended PX (PXe) domain, with two additional ␣-helices at the C terminus. We demonstrate that these ␣-helices are indispensible for the in vitro functions of SNX11. Sorting nexins (SNXs), which are proteins that contain a PX domain [3, 4, 6], are involved in several protein trafficking processes To this day, 33 SNXs have been identified.
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