2YOA

Synaptotagmin-1 C2B domain with phosphoserine

Summary for 2YOA

• Entry DOI: 10.2210/pdb2yoa/pdb
• Related: 1BYN 1K5W 1RSY 1TJM 1TJX 1UOV 1UOW
• Descriptor: SYNAPTOTAGMIN-1, CALCIUM ION, PHOSPHOSERINE, ... (5 entities in total)
• Functional Keywords: signaling protein
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Cellular location: Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass membrane protein : P21707
• Total number of polymer chains: 2
• Total formula weight: 35651.64

Authors

Honigmann, A.,van den Bogaart, G.,Iraheta, E.,Risselada, H.J.,Milovanovic, D.,Mueller, V.,Muellar, S.,Diederichsen, U.,Fasshauer, D.,Grubmuller, H.,Hell, S.W.,Eggeling, C.,Kuhnel, K.,Jahn, R. (deposition date: 2012-10-22, release date: 2013-03-20, Last modification date: 2023-12-20)

Primary citation

Honigmann, A.,Van Den Bogaart, G.,Iraheta, E.,Risselada, H.J.,Milovanovic, D.,Mueller, V.,Muellar, S.,Diederichsen, U.,Fasshauer, D.,Grubmuller, H.,Hell, S.W.,Eggeling, C.,Kuhnel, K.,Jahn, R.
Phosphatidylinositol 4,5-Bisphosphate Clusters Act as Molecular Beacons for Vesicle Recruitment
Nat.Struct.Mol.Biol., 20:679-, 2013

PubMed Abstract: 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.

PubMed: 23665582
DOI: 10.1038/NSMB.2570

Experimental method

X-RAY DIFFRACTION (1.5 Å)