4aei

From Proteopedia

(Difference between revisions)

Revision as of 05:31, 25 August 2022

Crystal structure of the AaHII-Fab4C1 complex

Structural highlights

4aei is a 9 chain structure with sequence from Androctonus australis hector and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	1seg, 1ptx, 1aho, 4aeh
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SCX2_ANDAU] Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals.

Publication Abstract from PubMed

The Old World scorpion Androctonus australis hector (Aah) produces one of the most lethal venoms for humans. Peptidic alpha-toxins AahI to AahIV are responsible for its potency, with AahII accounting for half of it. All four toxins are high affinity blockers of the fast inactivation phase of mammalian voltage-activated Na(+) channels. However, the high antigenic polymorphism of alpha-toxins prevents production of a polyvalent neutralizing antiserum, whereas the determinants dictating their trapping by neutralizing antibodies remain elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab) with high affinity and selectivity for AahII and solved a 2.3 A-resolution crystal structure of the complex. Sequestering of the C-terminal region of the bound toxin within a groove formed by the Fab combining loops is associated with a toxin orientation and main and side chain conformations that dictate the AahII antigenic specificity and efficient neutralization. From an anti-AahI mAb, we also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 A-resolution structure solved revealed a Fab molecule devoid of a bound AahI and with combining loops involved in packing interactions, denoting expulsion of the bound antigen upon crystal formation. Comparative analysis of the groove-like combining site of the toxin-bound anti-AahII Fab and planar combining surface of the unbound anti-AahI Fab along with complementary data from a flexible docking approach suggests occurrence of distinctive trapping orientations for the two toxins relative to their respective Fab. This study provides complementary templates for designing new molecules aimed at capturing Aah alpha-toxins and suitable for immunotherapy.

Structural Insights into Antibody Sequestering and Neutralizing of Na+ Channel alpha-Type Modulator from Old World Scorpion Venom.,Fabrichny IP, Mondielli G, Conrod S, Martin-Eauclaire MF, Bourne Y, Marchot P J Biol Chem. 2012 Apr 20;287(17):14136-48. Epub 2012 Feb 27. PMID:22371498^[1]

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

References

↑ Fabrichny IP, Mondielli G, Conrod S, Martin-Eauclaire MF, Bourne Y, Marchot P. Structural Insights into Antibody Sequestering and Neutralizing of Na+ Channel alpha-Type Modulator from Old World Scorpion Venom. J Biol Chem. 2012 Apr 20;287(17):14136-48. Epub 2012 Feb 27. PMID:22371498 doi:10.1074/jbc.M111.315382

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4aei"

@@ Line 3: / Line 3: @@
 <StructureSection load='4aei' size='340' side='right'caption='[[4aei]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4aei]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Androctonus_australis_hector Androctonus australis hector] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AEI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AEI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4aei]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Androctonus_australis_hector Androctonus australis hector] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AEI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1seg|1seg]], [[1ptx|1ptx]], [[1aho|1aho]], [[4aeh|4aeh]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1seg|1seg]], [[1ptx|1ptx]], [[1aho|1aho]], [[4aeh|4aeh]]</div></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=4aei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aei OCA], [http://pdbe.org/4aei PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4aei RCSB], [http://www.ebi.ac.uk/pdbsum/4aei PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4aei ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4aei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aei OCA], [https://pdbe.org/4aei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aei RCSB], [https://www.ebi.ac.uk/pdbsum/4aei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aei ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SCX2_ANDAU SCX2_ANDAU]] Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals.
+[[https://www.uniprot.org/uniprot/SCX2_ANDAU SCX2_ANDAU]] Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 ==See Also==
+*[[Hemolysin 3D structures|Hemolysin 3D structures]]
 *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
@@ Line 28: / Line 29: @@
 </StructureSection>
 [[Category: Androctonus australis hector]]
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
 [[Category: Bourne, Y]]

4aei

From Proteopedia

Revision as of 05:31, 25 August 2022

Crystal structure of the AaHII-Fab4C1 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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