3rmy: Difference between revisions
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[[ | ==Crystal structure of HCR/D W1238A mutant== | ||
<StructureSection load='3rmy' size='340' side='right' caption='[[3rmy]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3rmy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RMY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RMY FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n7j|3n7j]], [[3rmx|3rmx]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">botD, Botulinum Neurotoxin D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rmy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rmy RCSB], [http://www.ebi.ac.uk/pdbsum/3rmy PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. While several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle associated protein), the entry pathway of BoNT/D is less well understood. While BoNT/D entry is ganglioside dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study, BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing a ganglioside binding loop (GBL, residues Tyr1235-Ala1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp1238, located near the N terminus of the GBL, was mostly solvent inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2 (SV2). Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies. | |||
Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into neurons.,Kroken AR, Karalewitz AP, Fu Z, Kim JJ, Barbieri JT J Biol Chem. 2011 Jun 1. PMID:21632541<ref>PMID:21632541</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Clostridium botulinum]] | [[Category: Clostridium botulinum]] | ||
[[Category: Barbieri, J T.]] | [[Category: Barbieri, J T.]] | ||
Revision as of 04:54, 5 June 2014
Crystal structure of HCR/D W1238A mutant
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