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Synaptotagmin: Difference between revisions

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<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load='4npk' size='340' side='right' caption='Synaptostagmin-2 C2A and C2B domains complex with Ca+2 ions (green) (PDB code [[4npk]])' scene='80/802718/Cv/1'>
 
__TOC__
== Function ==
== Function ==


'''Synaptotagmin''' (SYT) are calcium-binding proteins which are conserved from nematodes to humans.  Fifteen SYTs have been identified in mammals<ref>PMID:18468511</ref>. '''Synaptotagmin-1''' (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions<ref>PMID:19412166</ref>.  The C2A domain of SYT binds phospholipids in Ca+2-dpendent manner<ref>PMID:9730811</ref>.  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<ref>PMID:7559535</ref>.  
'''Synaptotagmin''' (SYT) are calcium-binding proteins which are conserved from nematodes to humans.  Fifteen SYTs have been identified in mammals<ref>PMID:18468511</ref>. '''Synaptotagmin-1''' (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions<ref>PMID:19412166</ref>.  The C2A domain of SYT binds phospholipids in Ca+2-dependent manner<ref>PMID:9730811</ref>.  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<ref>PMID:7559535</ref>.  


== Disease ==
*'''Synaptotagmin-2''' is a Ca+2 sensor for fast neurotransmitter release in caudal brain regions<ref>PMID:17192432</ref>.
*'''Synaptotagmin-3''' is a Ca+2 sensor for fast neurotransmitter release in presynapses<ref>PMID:36261524</ref>.
*'''Synaptotagmin-4''' regulates membrane traffic in neurons<ref>PMID:31743468</ref>.
*'''Synaptotagmin-5''' is dense-core vesicle-specific controlling Ca+2-regulated secretion<ref>PMID:12006594</ref>.
*'''Synaptotagmin-7''' is a plasma membrane Ca+2 sensor in synaptic exocytosis<ref>PMID:11395007</ref>.
*'''Synaptotagmin-13''' is a Ca+2-independent regulator of endocrine cell aggression and islet formation<ref>PMID:35927244</ref>.
*'''Synaptotagmin-like proteins''' (SYTL) are required in a generation of a single apical surface per cell<ref>PMID:22820376</ref>.
*'''Synaptotagmin-like protein 4''' (SYTL4) is involved in intracellular membrane trafficking.


== Relevance ==
== Relevance ==


'''Synaptotagmin-4''' is up-regulated by chronic depolarization and seizures. '''Synaptotagmin-1''' is promising biomarker to monitor dysfunction and degeneration in Alzheimer disease<ref>PMID:27716408</ref>.  
'''Synaptotagmin-4''' is up-regulated by chronic depolarization and seizures. '''Synaptotagmin-1''' is a promising biomarker to monitor dysfunction and degeneration in Alzheimer disease<ref>PMID:27716408</ref>.  


== Structural highlights ==
== Structural highlights ==


At the tip of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by 5 aspartates and one serine.
SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the <scene name='80/802718/Cv/12'>C2A Ca+2-binding, C2B</scene>, 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<ref>PMID:24373768</ref>.
 
*<scene name='80/802718/Cv/8'>1st Ca+2 binding site</scene>. Water molecules are shown as red spheres.
</StructureSection>
*<scene name='80/802718/Cv/9'>2nd Ca+2 binding site</scene>.
*<scene name='80/802718/Cv/10'>3th Ca+2 binding site</scene>.
*<scene name='80/802718/Cv/11'>All Ca+2 binding sites</scene>.


==3D structures of synaptotagmin==
==3D structures of synaptotagmin==
[[Synaptotagmin 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Synaptotagmin-1; domains: toxin-binding 33-53; C2A 141-268; C2B 267-446
 
**[[3f00]], [[3f01]], [[3f04]], [[3f05]] – hSYT1 C2A domain – human <br />
**[[2k45]] – hSYT1 C2A domain - NMR<br />
**[[2r83]] – hSYT1 C2A+C2B domains  <br />
**[[5t0r]], [[5vfe]] – mSYT1 C2A domain – mouse <br />
**[[1rsy]], [[4wee]] – rSYT1 C2A domain – rat <br />
**[[1k5w]], [[1byn]] – rSYT1 C2A domain - NMR<br />
**[[1tjx]], [[1tjm]], [[1uov]], [[1uow]] – rSYT1 C2B domain <br />
**[[5ccj]] – rSYT1 C2B domain (mutant)  <br />
**[[5vff]], [[5vfg]], [[5t0s]] – mSYT1 C2B domain <br />
 
*Synaptotagmin-1 complex
 
**[[2lha]] – hSYT1 C2B domain + inositol hexaphosphate - NMR<br />
**[[2yoa]] – rSYT1 C2B domain + phosphoserine<br />
**[[4v11]] – hSYT1 C2B domain + synaptic vesicle glycoprotein peptide<br />
**[[2k4a]] – hSYT1 C2A domain + heparin-binding growth factor - NMR<br />
**[[2ki6]] – hSYT1 C2A domain + heparin-binding growth factor + protein S100 A13<br />
**[[4isq]] – hSYT1 toxin-binding domain + botulinum neurotoxin DC heavy chain<br />
**[[2n1t]] – hSYT1 C2B domain + VAMP-2 + syntaxin-1A + SNAP-25 <br />
**[[5w5d]], [[5w5c]] – rSYT1 C2B domain + VAMP-2 + syntaxin-1A + SNAP-25 + complexin-1<br />
**[[5cch]], [[5ccg]], [[5kj7]], [[5cci]], [[5kj8]] – rSYT1 C2A+C2B domains + VAMP-2 + syntaxin-1A + SNAP-25 <br />
 
*Synaptotagmin-2
 
**[[2np0]], [[4kbb]] – mSYT2 ectodomain 1-60 + botulinum neurotoxin B<br />
**[[4isr]] – rSYT2 toxin-binding domain + botulinum neurotoxin DC heavy chain<br />
**[[2nm1]] – rSYT2 toxin-binding domain + botulinum neurotoxin B receptor-binding domain<br />
**[[4npk]], [[4npj]] – hSYT2 C2A+C2B domains  363-662<br />
**[[4npi]] – hSYT2 SMP+C2A+C2B domains  191-662<br />
 
*Synaptotagmin-3
 
**[[3hn8]] – rSYT3 C2A+C2B domains 293-588 <br />
**[[1dqv]] – rSYT3 C2A+C2B domains - NMR<br />
 
*Synaptotagmin-4
 
**[[1ugk]] – hSYT4 C2A domain - NMR<br />
**[[1w15]], [[1w16]] – rSYT4 C2B domain<br />
 
*Synaptotagmin-5
 
**[[5h4y]] – hSYT5 C2A domain<br />
**[[5h4z]] – hSYT5 C2A domain (mutant)<br />
 
*Synaptotagmin-7
 
**[[2d8k]] – hSYT7 C2A domain - NMR<br />
**[[6anj]] – rSYT7 C2A domain  <br />
**[[3n5a]] – mSYT7 C2B domain 266-403 <br />
**[[6ank]] – rSYT7 C2A+C2B domains  <br />
 
*Synaptotagmin-13
 
**[[1wfm]] – hSYT13 C2A domain - NMR<br />
}}
 
 
 


== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky
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