Intracellular Vesicle Fusion Requires a Membrane-Destabilizing Peptide Located at the Juxtamembrane Region of the v-SNARE.

Shailendra S Rathore, Yinghui Liu, Haijia Yu, Chun Wan, MyeongSeon Lee, Qian Yin, Michael H B Stowell, Jingshi Shen

Cell reports 2019 Dec 24

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Intracellular vesicle fusion is mediated by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18 (SM) proteins. It is generally accepted that membrane fusion occurs when the vesicle and target membranes are brought into close proximity by SNAREs and SM proteins. In this work, we demonstrate that, for fusion to occur, membrane bilayers must be destabilized by a conserved membrane-embedded motif located at the juxtamembrane region of the vesicle-anchored v-SNARE. Comprised of basic and hydrophobic residues, the juxtamembrane motif perturbs the lipid bilayer structure and promotes SNARE-SM-mediated membrane fusion. The juxtamembrane motif can be functionally substituted with an unrelated membrane-disrupting peptide in the membrane fusion reaction. These findings establish the juxtamembrane motif of the v-SNARE as a membrane-destabilizing peptide. Requirement of membrane-destabilizing peptides is likely a common feature of biological membrane fusion. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Shailendra S Rathore, Yinghui Liu, Haijia Yu, Chun Wan, MyeongSeon Lee, Qian Yin, Michael H B Stowell, Jingshi Shen. Intracellular Vesicle Fusion Requires a Membrane-Destabilizing Peptide Located at the Juxtamembrane Region of the v-SNARE. Cell reports. 2019 Dec 24;29(13):4583-4592.e3