Structure of a Membrane Tethering Complex Incorporating Multiple SNAREs

Abstract

Most membrane fusion reactions in eukaryotic cells are mediated by membrane tethering 17 complexes (MTCs) and SNARE proteins. MTCs are much larger than SNAREs and are thought 18 to mediate the initial attachment of two membranes. Complementary SNAREs then form 19 membrane-bridging complexes whose assembly draws the membranes together for fusion. Here, 20 we present a cryo-EM structure of the simplest known MTC, the 255-kDa Dsl1 complex, bound 21 to the two SNAREs that anchor it to the endoplasmic reticulum. N-terminal domains of the 22 SNAREs form an integral part of the structure, stabilizing a Dsl1 complex configuration with 23 remarkable and unexpected similarities to the 850-kDa exocyst MTC. The structure of the 24 SNARE-anchored Dsl1 complex and its comparison with exocyst reveal what are likely to be 25 common principles underlying MTC function.