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PDBsum entry 2yoa
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Signaling protein
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PDB id
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2yoa
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References listed in PDB file
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Key reference
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Title
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Phosphatidylinositol 4,5-Bisphosphate clusters act as molecular beacons for vesicle recruitment.
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Authors
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A.Honigmann,
G.Van den bogaart,
E.Iraheta,
H.J.Risselada,
D.Milovanovic,
V.Mueller,
S.Müllar,
U.Diederichsen,
D.Fasshauer,
H.Grubmüller,
S.W.Hell,
C.Eggeling,
K.Kühnel,
R.Jahn.
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Ref.
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Nat Struct Biol, 2013,
20,
679-686.
[DOI no: ]
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PubMed id
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Abstract
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Synaptic-vesicle exocytosis is mediated by the vesicular Ca(2+) sensor
synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A
and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2).
However, it is unclear how these interactions contribute to triggering membrane
fusion. Using PC12 cells from Rattus norvegicus and artificial supported
bilayers, we show that synaptotagmin-1 interacts with the polybasic linker
region of syntaxin-1A independent of Ca(2+) through PIP2. This interaction
allows both Ca(2+)-binding sites of synaptotagmin-1 to bind to
phosphatidylserine in the vesicle membrane upon Ca(2+) triggering. We determined
the crystal structure of the C2B domain of synaptotagmin-1 bound to
phosphoserine, allowing development of a high-resolution model of synaptotagmin
bridging two different membranes. Our results suggest that PIP2 clusters
organized by syntaxin-1 act as molecular beacons for vesicle docking, with the
subsequent Ca(2+) influx bringing the vesicle membrane close enough for membrane
fusion.
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