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
Affiliations
Shailendra S. Rathore
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA
Yinghui Liu
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Haijia Yu
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China; Corresponding author
Chun Wan
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA
MyeongSeon Lee
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA
Qian Yin
Department of Biological Sciences and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA
Michael H.B. Stowell
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA
Jingshi Shen
Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309, USA; Corresponding author
Summary: 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. : Membrane fusion occurs when the vesicle and target membranes are brought into close proximity by SNAREs and SM proteins. In this work, Rathore et al. 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.
