The Ang2 subunit of GARP interacts with the Habc domains of Stx6 and Stx10
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The crystal structure of the Stx6-Ang2 complex reveals a distinct binding mode
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A LxxYY motif in Ang2 binds to a DPF[...]R motif in Stx6
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The Ang2 interaction with Stx6 and Stx10 suggests a mutually exclusive engagement
Summary
The Golgi-Associated Retrograde Protein (GARP) complex is a tethering factor involved in the fusion of endosome-derived transport vesicles to the trans-Golgi network through interaction with components of the Syntaxin 6/Syntaxin 16/Vti1a/VAMP4 SNARE complex. The mechanisms by which GARP and other tethering factors engage the SNARE fusion machinery are poorly understood. Herein, we report the structural basis for the interaction of the human Ang2 subunit of GARP with the Syntaxin 6 and the closely related Syntaxin 10. The crystal structure of the Syntaxin 6 Habc domain in complex with a peptide from the N terminus of Ang2 shows a binding mode in which a dityrosine motif of Ang2 interacts with a highly conserved groove in Syntaxin 6. Structure-based mutational analyses validate the crystal structure and support the phylogenetic conservation of this interaction.
