2ndb: Difference between revisions

Revision as of 10:27, 13 September 2017

NMR structure of omega-agatoxin IVA in DPC micelles

Structural highlights

2ndb is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TOG4A_AGEAP] Omega-agatoxins inhibit neuronal voltage-gated calcium channels. This toxin acts by modifying the gating of the high voltage activated P-type Cav2.1/CACNA1A channel. Is a potent blocker in both insect and mammalian central neurons.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

To analyze structural features of omega-Aga IVA, a gating modifier toxin from spider venom, we here investigated the NMR solution structure of omega-Aga IVA within DPC micelles. Under those conditions, the Cys-rich central region of omega-Aga IVA still retains the inhibitor Cys knot motif with three short antiparallel beta-strands seen in water. However, 15N HSQC spectra of omega-Aga IVA within micelles revealed that there are radical changes to the toxin's C-terminal tail and several loops upon binding to micelles. The C-terminal tail of omega-Aga IVA appears to assume a beta-turn like conformation within micelles, though it is disordered in water. Whole-cell patch clamp studies with several omega-Aga IVA analogs indicate that both the hydrophobic C-terminal tail and an Arg patch in the core region of omega-Aga IVA are critical for Cav2.1 blockade. These results suggest that the membrane environment stabilizes the structure of the toxin, enabling it to act in a manner similar to other gating modifier toxins, though its mode of interaction with the membrane and the channel is unique.

Structure-activity relationships of omega-Agatoxin IVA in lipid membranes.,Ryu JH, Jung HJ, Konishi S, Kim HH, Park ZY, Kim JI Biochem Biophys Res Commun. 2017 Jan 1;482(1):170-175. doi:, 10.1016/j.bbrc.2016.11.025. Epub 2016 Nov 9. PMID:27838299^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME. P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature. 1992 Feb 27;355(6363):827-9. PMID:1311418 doi:https://dx.doi.org/10.1038/355827a0
↑ Nishio H, Kumagaye KY, Kubo S, Chen YN, Momiyama A, Takahashi T, Kimura T, Sakakibara S. Synthesis of omega-agatoxin IVA and its related peptides. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1447-53. PMID:8250902 doi:https://dx.doi.org/10.1006/bbrc.1993.2414
↑ Bickmeyer U, Rossler W, Wiegand H. Omega AGA toxin IVA blocks high-voltage-activated calcium channel currents in cultured pars intercerebralis neurosecretory cells of adult locusta migratoria. Neurosci Lett. 1994 Nov 7;181(1-2):113-6. PMID:7898748
↑ McDonough SI, Mintz IM, Bean BP. Alteration of P-type calcium channel gating by the spider toxin omega-Aga-IVA. Biophys J. 1997 May;72(5):2117-28. PMID:9129813 doi:https://dx.doi.org/10.1016/S0006-3495(97)78854-4
↑ Wicher D, Penzlin H. Ca2+ currents in central insect neurons: electrophysiological and pharmacological properties. J Neurophysiol. 1997 Jan;77(1):186-99. PMID:9120560
↑ Winterfield JR, Swartz KJ. A hot spot for the interaction of gating modifier toxins with voltage-dependent ion channels. J Gen Physiol. 2000 Nov;116(5):637-44. PMID:11055992
↑ Wang XH, Connor M, Wilson D, Wilson HI, Nicholson GM, Smith R, Shaw D, Mackay JP, Alewood PF, Christie MJ, King GF. Discovery and structure of a potent and highly specific blocker of insect calcium channels. J Biol Chem. 2001 Oct 26;276(43):40306-12. Epub 2001 Aug 24. PMID:11522785 doi:https://dx.doi.org/10.1074/jbc.M105206200
↑ Ryu JH, Jung HJ, Konishi S, Kim HH, Park ZY, Kim JI. Structure-activity relationships of omega-Agatoxin IVA in lipid membranes. Biochem Biophys Res Commun. 2017 Jan 1;482(1):170-175. doi:, 10.1016/j.bbrc.2016.11.025. Epub 2016 Nov 9. PMID:27838299 doi:https://dx.doi.org/10.1016/j.bbrc.2016.11.025

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OCA

[1] Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME. P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature. 1992 Feb 27;355(6363):827-9. PMID:1311418 doi:https://dx.doi.org/10.1038/355827a0

[2] Nishio H, Kumagaye KY, Kubo S, Chen YN, Momiyama A, Takahashi T, Kimura T, Sakakibara S. Synthesis of omega-agatoxin IVA and its related peptides. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1447-53. PMID:8250902 doi:https://dx.doi.org/10.1006/bbrc.1993.2414

[3] Bickmeyer U, Rossler W, Wiegand H. Omega AGA toxin IVA blocks high-voltage-activated calcium channel currents in cultured pars intercerebralis neurosecretory cells of adult locusta migratoria. Neurosci Lett. 1994 Nov 7;181(1-2):113-6. PMID:7898748

[4] McDonough SI, Mintz IM, Bean BP. Alteration of P-type calcium channel gating by the spider toxin omega-Aga-IVA. Biophys J. 1997 May;72(5):2117-28. PMID:9129813 doi:https://dx.doi.org/10.1016/S0006-3495(97)78854-4

[5] Wicher D, Penzlin H. Ca2+ currents in central insect neurons: electrophysiological and pharmacological properties. J Neurophysiol. 1997 Jan;77(1):186-99. PMID:9120560

[6] Winterfield JR, Swartz KJ. A hot spot for the interaction of gating modifier toxins with voltage-dependent ion channels. J Gen Physiol. 2000 Nov;116(5):637-44. PMID:11055992

[7] Wang XH, Connor M, Wilson D, Wilson HI, Nicholson GM, Smith R, Shaw D, Mackay JP, Alewood PF, Christie MJ, King GF. Discovery and structure of a potent and highly specific blocker of insect calcium channels. J Biol Chem. 2001 Oct 26;276(43):40306-12. Epub 2001 Aug 24. PMID:11522785 doi:https://dx.doi.org/10.1074/jbc.M105206200

[8] Ryu JH, Jung HJ, Konishi S, Kim HH, Park ZY, Kim JI. Structure-activity relationships of omega-Agatoxin IVA in lipid membranes. Biochem Biophys Res Commun. 2017 Jan 1;482(1):170-175. doi:, 10.1016/j.bbrc.2016.11.025. Epub 2016 Nov 9. PMID:27838299 doi:https://dx.doi.org/10.1016/j.bbrc.2016.11.025

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 2ndb is ON HOLD  until Paper Publication
+==NMR structure of omega-agatoxin IVA in DPC micelles==
+<StructureSection load='2ndb' size='340' side='right' caption='[[2ndb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2ndb]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NDB FirstGlance]. <br>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ndb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ndb OCA], [http://pdbe.org/2ndb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ndb RCSB], [http://www.ebi.ac.uk/pdbsum/2ndb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ndb ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TOG4A_AGEAP TOG4A_AGEAP]] Omega-agatoxins inhibit neuronal voltage-gated calcium channels. This toxin acts by modifying the gating of the high voltage activated P-type Cav2.1/CACNA1A channel. Is a potent blocker in both insect and mammalian central neurons.<ref>PMID:1311418</ref> <ref>PMID:8250902</ref> <ref>PMID:7898748</ref> <ref>PMID:9129813</ref> <ref>PMID:9120560</ref> <ref>PMID:11055992</ref> <ref>PMID:11522785</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+To analyze structural features of omega-Aga IVA, a gating modifier toxin from spider venom, we here investigated the NMR solution structure of omega-Aga IVA within DPC micelles. Under those conditions, the Cys-rich central region of omega-Aga IVA still retains the inhibitor Cys knot motif with three short antiparallel beta-strands seen in water. However, 15N HSQC spectra of omega-Aga IVA within micelles revealed that there are radical changes to the toxin's C-terminal tail and several loops upon binding to micelles. The C-terminal tail of omega-Aga IVA appears to assume a beta-turn like conformation within micelles, though it is disordered in water. Whole-cell patch clamp studies with several omega-Aga IVA analogs indicate that both the hydrophobic C-terminal tail and an Arg patch in the core region of omega-Aga IVA are critical for Cav2.1 blockade. These results suggest that the membrane environment stabilizes the structure of the toxin, enabling it to act in a manner similar to other gating modifier toxins, though its mode of interaction with the membrane and the channel is unique.
-Authors: Ryu,, J., Kim, J.
+Structure-activity relationships of omega-Agatoxin IVA in lipid membranes.,Ryu JH, Jung HJ, Konishi S, Kim HH, Park ZY, Kim JI Biochem Biophys Res Commun. 2017 Jan 1;482(1):170-175. doi:, 10.1016/j.bbrc.2016.11.025. Epub 2016 Nov 9. PMID:27838299<ref>PMID:27838299</ref>
-Description: NMR structure of omega-agatoxin IVA in DPC micelles
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Kim, J]]
+<div class="pdbe-citations 2ndb" style="background-color:#fffaf0;"></div>
-[[Category: Ryu,, J]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Kim, J I]]
+[[Category: Ryu, J H]]
+[[Category: Neurotoxin]]
+[[Category: Toxin]]

2ndb: Difference between revisions

Revision as of 10:27, 13 September 2017

NMR structure of omega-agatoxin IVA in DPC micelles

Structural highlights

Function

Publication Abstract from PubMed

References

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