These authors contributed equally to this work.
Defined Subunit Arrangement and Rab Interactions Are Required for Functionality of the HOPS Tethering Complex
Article first published online: 5 JUL 2010
© 2010 John Wiley & Sons A/S
Volume 11, Issue 10, pages 1334–1346, October 2010
How to Cite
Ostrowicz, C. W., Bröcker, C., Ahnert, F., Nordmann, M., Lachmann, J., Peplowska, K., Perz, A., Auffarth, K., Engelbrecht-Vandré, S. and Ungermann, C. (2010), Defined Subunit Arrangement and Rab Interactions Are Required for Functionality of the HOPS Tethering Complex. Traffic, 11: 1334–1346. doi: 10.1111/j.1600-0854.2010.01097.x
- Issue published online: 8 SEP 2010
- Article first published online: 5 JUL 2010
- Received 7 May 2010, revised and accepted for publication 29 June 2010, uncorrected manuscript published online 5 July 2010, published online 1 August 2010
Within the endomembrane system of eukaryotic cells, multisubunit tethering complexes together with their corresponding Rab-GTPases coordinate vesicle tethering and fusion. Here, we present evidence that two homologous hexameric tethering complexes, the endosomal CORVET (Class C core vacuole/endosome transport) and the vacuolar HOPS (homotypic vacuole fusion and protein sorting) complex, have similar subunit topologies. Both complexes contain two Rab-binding proteins at one end, and the Sec1/Munc18-like Vps33 at the opposite side, suggesting a model on membrane bridging via Rab-GTP and SNARE binding. In agreement, HOPS activity can be reconstituted using purified subcomplexes containing the Rab and Vps33 module, but requires all six subunits for activity. At the center of HOPS and CORVET, the class C proteins Vps11 and Vps18 connect the two parts, and Vps11 binds both HOPS Vps39 and CORVET Vps3 via the same binding site. As HOPS Vps39 is also found at endosomes, our data thus suggest that these tethering complexes follow defined but distinct assembly pathways, and may undergo transition by simple subunit interchange.