Structural studies of SNARE complex and its interaction with complexin by molecular dynamics simulation.
Since neurotransmitter releasing into the synaptic space delivers electrical signals from presynaptic neural cell to the postsynaptic cell, neurotransmitter secretion must be much orchestrated. Crowded intracellular vesicles involving neurotransmitters present a question of the how secretory vesicles fuse onto the plasma membrane in a fast synchronized fashion. Complexin is one of the most experimentally studied proteins that regulate assembly of fusogenic four-helix SNARE complex to synchronized neurotransmitter secretion. We used MD simulation to investigate the interaction of complexin with the neural SNARE complex in detail. Our results show that the SNARE complex interacts with the complexin central helix by forming salt bridges and hydrogen bonds. Complexin also can interact with the Q-SNARE complex instead of synaptobrevin to decrease the Q-SNARE flexibility. The complexin alpha-accessory helix and the C-terminal region of synaptobrevin can interact with the same region of syntaxin. Although the alpha-accessory helix aids the tight binding of the central helix to the SNARE complex, its proximity with synaptobrevin causes the destabilization of syntaxin and Sn1 helices. This study suggests that the alpha-accessory helix of complexin can be an inhibiting factor for membrane fusion by competing with synaptobrevin for binding to the Q-SNARE complex.
Ghahremanpour
Mohammad Mehdi
MM
Department of Cellular and Molecular Biology, Faculty of Science, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
Mehrnejad
Faramarz
F
Moghaddam
Majid Erfani
ME
D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000737:chemistry; D003198:Computer Simulation; D004331:Drosophila melanogaster; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D018377:Neurotransmitter Agents / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D050682:Q-SNARE Proteins / Q000737:chemistry*; D050765:Qa-SNARE Proteins / Q000737:chemistry; D050683:R-SNARE Proteins / Q000737:chemistry; D051381:Rats; D017386:Sequence Homology, Amino Acid
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050682:Q-SNARE Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C095992:complexin I; D002118:Calcium