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| <StructureSection load='5lob' size='340' side='right' caption='Structure of glycosylated California poppy reticuline oxidase complex with reticuline and FAD (PDB code [[5lob]])' scene=''> | | <StructureSection load='5lob' size='340' side='right' caption='Structure of rabphilin-3A C2B domain (green, grey, pink) complex with SNAP-25 N-terminal helix (yellow, magenta), glycerol, sulfate and Ca+2 ions (PDB code [[5lob]])' scene=''> |
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| == Function == | | == Function == |
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| == Structural highlights == | | == Structural highlights == |
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| The 3D structure of the complex between RO and its substrate reticuline show the cofactor FAD having bicovalent attachment to RO His and Cys. The substrate reticuline is seen in the active site cavity interacting with FAD and numerous RO sidechains<ref>PMID:18953357</ref>. | | The 3D structure of the complex between three Rab C2B domains and a 4-helix bundle belonging to two SNAP-25 monomers. Two different helix-helix interactions between Rab and SNAP-25 are seen. One involves 2 monomers of SNAP-25 and the other involves one monomer<ref>PMID:28634303</ref>. |
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| </StructureSection> | | </StructureSection> |
Revision as of 10:06, 4 February 2021
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Function
Rabphilin (Rab) is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites[1].
Relevance
Rab is a major auto antigen in lymphocytic infundibulo-neurohypophysitis (LINH). Antibodies to Rab may serve as a biomarker for the diagnosis of LINH[2].
Structural highlights
The 3D structure of the complex between three Rab C2B domains and a 4-helix bundle belonging to two SNAP-25 monomers. Two different helix-helix interactions between Rab and SNAP-25 are seen. One involves 2 monomers of SNAP-25 and the other involves one monomer[3].
- ↑ Stanic J, Carta M, Eberini I, Pelucchi S, Marcello E, Genazzani AA, Racca C, Mulle C, Di Luca M, Gardoni F. Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex. Nat Commun. 2015 Dec 18;6:10181. doi: 10.1038/ncomms10181. PMID:26679993 doi:https://dx.doi.org/10.1038/ncomms10181
- ↑ Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y. Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. J Clin Endocrinol Metab. 2015 Jul;100(7):E946-54. doi: 10.1210/jc.2014-4209. Epub, 2015 Apr 28. PMID:25919460 doi:https://dx.doi.org/10.1210/jc.2014-4209
- ↑ Ferrer-Orta C, Perez-Sanchez MD, Coronado-Parra T, Silva C, Lopez-Martinez D, Baltanas-Copado J, Gomez-Fernandez JC, Corbalan-Garcia S, Verdaguer N. Structural characterization of the Rabphilin-3A-SNAP25 interaction. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5343-E5351. doi:, 10.1073/pnas.1702542114. Epub 2017 Jun 20. PMID:28634303 doi:https://dx.doi.org/10.1073/pnas.1702542114
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3D Structures of rabphilin 3-A
Updated on 04-February-2021
Domains: C2A 378-510; C2B 541-680
2cm5, 2cm6 – rRab C2B domain – rat
4izk – rRab C2B domain - NMR
5lo8 – rRab C2B domain + inositol phosphate derivative
5lob, 5low – rRab C2B domain + SNAP25
2chd, 4lt7 – rRab C2A domain
4np9, 4ns0 – rRab C2A domain + inositol phosphate derivative
1zbd – rRab 19-217 (mutant) + rRab effector domain 40-179 (mutant) + GTP
2k3h – mRab C2A domain - mouse - NMR
References
