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bioRxiv · 10.1101/2021.12.20.473486

Structure of a TRAPPII-Rab11 activation intermediate reveals GTPase substrate selection mechanisms

Bagde, S. R.·Fromme, J. C.
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Abstract

Rab1 and Rab11 are essential regulators of the eukaryotic secretory and endocytic recycling pathways. The TRAPP complexes activate these GTPases via nucleotide exchange using a shared set of core subunits. The basal specificity of the TRAPP core is towards Rab1, yet the TRAPPII complex is specific for Rab11. A steric gating mechanism has been proposed to explain TRAPPII counterselection against Rab1. Here we present cryoEM structures of the 22-subunit TRAPPII complex from budding yeast, including a TRAPPII-Rab11 nucleotide exchange intermediate. The Trs130 subunit provides a "leg" that positions the active site distal to the membrane surface, and this leg is required for steric gating. The related TRAPPIII complex is unable to activate Rab11 due to a repulsive interaction, which TRAPPII surmounts using the Trs120 subunit as a "lid" to enclose the active site. TRAPPII also adopts an open conformation enabling Rab11 to access and exit from the active site chamber.

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Bagde, S. R., Fromme, J. C.. 2021-12-20. Structure of a TRAPPII-Rab11 activation intermediate reveals GTPase substrate selection mechanisms. https://doi.org/10.1101/2021.12.20.473486

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