Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Structural basis for the Munc18 and Syntaxin interactions implicated for regulation of membrane trafficking (#181)

Shu-Hong Hu 1 , Michelle P Christie 1 , Russell J Jarrott 1 , Andrew E Whitten 1 , Asma Rehman 1 , Gordon J King 1 , Brett M Collins 1 , Jennifer L Martin 1
  1. Griffith University, Nathan, QLD, Australia

The Sec1/Munc18 (SM) proteins and the Soluble N-ethymaleimide-sensitive factor Attachment protein REceptors (SNAREs) play an essential role in membrane trafficking. The SNARE complex is composed of the target membrane SNAREs (t-SNAREs Sx and SNAP) and the vesicle membrane SNARE (v-SNARE VAMP). The formation of the SNARE complex leads to membrane fusion. Three mammalian SM proteins (Munc18a, Munc18b and Munc18c) regulate vesicle transport to the plasma membrane. Neuronal Munc18a is essential for neurotransmission release and binds specifically to its cognate Sx1a. Munc18c binds to Sx4, involved in insulin-regulated trafficking of glucose transporter (GLUT4). Structural studies have revealed the two binding modes of the interaction between Munc18a and Sx1a (N-terminal peptide and “closed”) (1, 2). The Munc18a/Sx1a crystal structure showed that Munc18a binds to Sx1a in a closed conformation that is incompatible with SNARE complex formation (3) We solved the crystal structure of GLUT4-associated Munc18c in complex with Sx4 N-peptide, providing structural evidence for the positive regulatory role of Munc18 in facilitating vesicle trafficking (4). We also obtained the crystal structure of neuronal Munc18a bound to a non-cognate Sx4 N-peptide (5). Furthermore, our recent results have showed that Munc18a binds to both Sx1a and Sx4, though it interacts more tightly with Sx1a. Munc18c interacts with both Sx4 and Sx1a, and apparently binds Sx1a a little more tightly than it binds Sx4 (6).