Crystal structure of bet3 reveals a novel mechanism for Golgi localization of tethering factor TRAPP

Abstract

Transport protein particle (TRAPP) is a large multiprotein complex involved in endoplasmic reticulum-to-Golgi and intra-Golgi traffic. TRAPP specifically and persistently resides on Golgi membranes. Neither the mechanism of the subcellular localization nor the function of any of the individual TRAPP components is known. Here, the crystal structure of mouse Bet3p (bet3), a conserved TRAPP component, reveals a dimeric structure with hydrophobic channels. The channel entrances are located on a putative membrane-interacting surface that is distinctively flat, wide and decorated with positively charged residues. Charge-inversion mutations on the flat surface of the highly conserved yeast Bet3p led to conditional lethality, incorrect localization and membrane trafficking defects. A channel-blocking mutation led to similar defects. These data delineate a molecular mechanism of Golgi-specific targeting and anchoring of Bet3p involving the charged surface and insertion of a Golgi-specific hydrophobic moiety into the channels. This essential subunit could then direct other TRAPP components to the Golgi.