Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

The role of Munc18 domain 3a in SNARE complex formation  (#203)

Emma K Livingstone 1 , Michelle P Christie 1 , Saroja Weeratunga 1 , Jennifer L Martin 1 2 , Brett M Collins 1
  1. Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia
  2. The Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia

Vesicle membrane fusion is essential for neurotransmission and blood glucose control, dysfunction of which is associated with neurological disorders and diabetes.1-2 The membrane fusion machinery, the topic of the 2013 Nobel Prize in Physiology or Medicine, comprises the soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), and the Sec1/Munc18 (SM) proteins.3 Cognate SNAREs from vesicle and target membranes associate to form a trans-SNARE complex. SNARE complex formation provides energy to drive membrane fusion and confers the necessary specificity for regulated delivery of cellular cargo. The SM protein family has been implicated in the regulation of SNARE complex assembly, although their precise regulatory role is controversial.4 Recent work on an SM protein involved in yeast homotypic fusion suggests that SM proteins may act as templates, orchestrating the alignment of SNAREs from the vesicle and target membranes, promoting membrane fusion.5 Here we describe recent progress towards the translation of these findings to the mammalian Munc18a and Munc18c proteins, which function in neurotransmission and blood glucose control respectively.

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  5. Baker, R. W.; Jeffrey, P. D.; Zick, M.; Phillips, B. P.; Wickner, W. T.; Hughson, F. M., A direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly. Science 2015, 349 (6252), 1111-1114.