Description:
<jats:p>The Sec1/Munc18 (<jats:styled-content style="fixed-case">SM</jats:styled-content>) proteins constitute a conserved family with essential functions in <jats:styled-content style="fixed-case">SNARE</jats:styled-content>‐mediated membrane fusion. Recently, a new protein–protein interaction site in Sec1p, designated the groove, was proposed. Here, we show that a <jats:italic>sec1</jats:italic> groove mutant yeast strain, <jats:italic>sec1(w24)</jats:italic>, displays temperature‐sensitive growth and secretion defects. The yeast Sec1p and mammalian Munc18‐1 grooves were shown to play an important role in the interaction with the <jats:styled-content style="fixed-case">SNAREs</jats:styled-content> Sec9p and <jats:styled-content style="fixed-case">SNAP</jats:styled-content>‐25b, respectively. Incubation of <jats:styled-content style="fixed-case">SNAP</jats:styled-content>‐25b with the Munc18‐1 groove mutant resulted in a lag in the kinetics of <jats:styled-content style="fixed-case">SNARE</jats:styled-content> complex assembly <jats:italic>in vitro</jats:italic> when compared with wild‐type Munc18‐1. The <jats:styled-content style="fixed-case">SNARE</jats:styled-content> regulator <jats:italic><jats:styled-content style="fixed-case">SRO7</jats:styled-content></jats:italic> was identified as a multicopy suppressor of <jats:italic>sec1(w24</jats:italic>) groove mutant and an intact Sec1p groove was required for the plasma membrane targeting of Sro7p–<jats:styled-content style="fixed-case">SNARE</jats:styled-content> complexes. Simultaneous inactivation of Sec1p groove and <jats:italic><jats:styled-content style="fixed-case">SRO7</jats:styled-content></jats:italic> resulted in reduced levels of exocytic <jats:styled-content style="fixed-case">SNARE</jats:styled-content> complexes. Our results identify the groove as a conserved interaction surface in <jats:styled-content style="fixed-case">SM</jats:styled-content> proteins. The results indicate that this structural element is important for interactions with Sec9p/<jats:styled-content style="fixed-case">SNAP</jats:styled-content>‐25 and participates, in concert with Sro7p, in the initial steps of <jats:styled-content style="fixed-case">SNARE</jats:styled-content> complex assembly.</jats:p><jats:p><jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tra12349-gra-0001.png" xlink:title="image" /></jats:p>