Synaptotagmin

Function Synaptotagmin (SYT) are calcium-binding proteins which are conserved from nematodes to humans. Fifteen SYTs have been identified in mammals. Synaptotagmin-1 (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions. The C2A domain of SYT binds phospholipids in Ca+2-dependent manner. The C2B domain of SYT promotes binding to other C2B domains and to accessory proteins. Ca+2 binding causes intramolecular association of domains C2A and C2B. The synaptic fusion apparatus includes the affinity between SYT and Syntaxin-1, This affinity increases by ca. 2 orders of magnitude upon binding of Ca+2. Relevance Synaptotagmin-4 is up-regulated by chronic depolarization and seizures. Synaptotagmin-1 is a promising biomarker to monitor dysfunction and degeneration in Alzheimer disease. Structural highlights SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the , spacer and C2C domains. At the cup-shaped cavity at the of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by canonical 5 aspartates. . Water molecules shown as red spheres. . . .

spinqualitylabelsall models Synaptostagmin-2 C2A and C2B domains complex with Ca+2 ions (green) (PDB code 4npk) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D structures of synaptotagmin3D structures of synaptotagmin

Updated on 06-December-2018

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• Synaptotagmin-1; domains: toxin-binding 33-53; C2A 141-268; C2B 267-446
  • 3f00, 3f01, 3f04, 3f05 – hSYT1 C2A domain – human
    
  • 2k45 – hSYT1 C2A domain - NMR
    
  • 2r83 – hSYT1 C2A+C2B domains
    
  • 5t0r, 5vfe – mSYT1 C2A domain – mouse
    
  • 1rsy, 4wee – rSYT1 C2A domain – rat
    
  • 1k5w, 1byn – rSYT1 C2A domain - NMR
    
  • 1tjx, 1tjm, 1uov, 1uow – rSYT1 C2B domain
    
  • 5ccj – rSYT1 C2B domain (mutant)
    
  • 5vff, 5vfg, 5t0s – mSYT1 C2B domain
    
• Synaptotagmin-1 complex
  • 2lha – hSYT1 C2B domain + inositol hexaphosphate - NMR
    
  • 2yoa – rSYT1 C2B domain + phosphoserine
    
  • 4v11 – hSYT1 C2B domain + synaptic vesicle glycoprotein peptide
    
  • 2k4a – hSYT1 C2A domain + heparin-binding growth factor - NMR
    
  • 2ki6 – hSYT1 C2A domain + heparin-binding growth factor + protein S100 A13
    
  • 4isq – hSYT1 toxin-binding domain + botulinum neurotoxin DC heavy chain
    
  • 2n1t – hSYT1 C2B domain + VAMP-2 + syntaxin-1A + SNAP-25
    
  • 5w5d, 5w5c – rSYT1 C2B domain + VAMP-2 + syntaxin-1A + SNAP-25 + complexin-1
    
  • 5cch, 5ccg, 5kj7, 5cci, 5kj8 – rSYT1 C2A+C2B domains + VAMP-2 + syntaxin-1A + SNAP-25
    
• Synaptotagmin-2
  • 2np0, 4kbb – mSYT2 ectodomain 1-60 + botulinum neurotoxin B
    
  • 4isr – rSYT2 toxin-binding domain + botulinum neurotoxin DC heavy chain
    
  • 2nm1 – rSYT2 toxin-binding domain + botulinum neurotoxin B receptor-binding domain
    
  • 4npk, 4npj – hSYT2 C2A+C2B domains 363-662
    
  • 4npi – hSYT2 SMP+C2A+C2B domains 191-662
    
• Synaptotagmin-3
  • 3hn8 – rSYT3 C2A+C2B domains 293-588
    
  • 1dqv – rSYT3 C2A+C2B domains - NMR
    
• Synaptotagmin-4
  • 1ugk – hSYT4 C2A domain - NMR
    
  • 1w15, 1w16 – rSYT4 C2B domain
    
• Synaptotagmin-5
  • 5h4y – hSYT5 C2A domain
    
  • 5h4z – hSYT5 C2A domain (mutant)
    
• Synaptotagmin-7
  • 2d8k – hSYT7 C2A domain - NMR
    
  • 6anj – rSYT7 C2A domain
    
  • 3n5a – mSYT7 C2B domain 266-403
    
  • 6ank – rSYT7 C2A+C2B domains
    
• Synaptotagmin-13
  • 1wfm – hSYT13 C2A domain - NMR