7k7d: Difference between revisions
New page: '''Unreleased structure''' The entry 7k7d is ON HOLD until Paper Publication Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Rodnin, M.V., Ladokhin, A.S. Description: Crystal st... |
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==Crystal structure of diphtheria toxin from crystals obtained at pH 6.0== | |||
<StructureSection load='7k7d' size='340' side='right'caption='[[7k7d]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K7D FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</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=7k7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k7d OCA], [https://pdbe.org/7k7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k7d RCSB], [https://www.ebi.ac.uk/pdbsum/7k7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k7d ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Diphtheria toxin, an exotoxin secreted by Corynebacterium that causes disease in humans by inhibiting protein synthesis, enters the cell via receptor-mediated endocytosis. The subsequent endosomal acidification triggers a series of conformational changes, resulting in the refolding and membrane insertion of the translocation (T-)domain and ultimately leading to the translocation of the catalytic domain into the cytoplasm. Here, we use X-ray crystallography along with circular dichroism and fluorescence spectroscopy to gain insight into the mechanism of the early stages of pH-dependent conformational transition. For the first time, we present the high-resolution structure of the diphtheria toxin at a mildly acidic pH (5-6) and compare it to the structure at neutral pH (7). We demonstrate that neither catalytic nor receptor-binding domains change their structure upon this acidification, while the T-domain undergoes a conformational change that results in the unfolding of the TH2-3 helices. Surprisingly, the TH1 helix maintains its conformation in the crystal of the full-length toxin even at pH 5. This contrasts with the evidence from the new and previously published data, obtained by spectroscopic measurements and molecular dynamics computer simulations, which indicate the refolding of TH1 upon the acidification of the isolated T-domain. The overall results imply that the membrane interactions of the T-domain are critical in ensuring the proper conformational changes required for the preparation of the diphtheria toxin for the cellular entry. | |||
Structure of the Diphtheria Toxin at Acidic pH: Implications for the Conformational Switching of the Translocation Domain.,Rodnin MV, Kashipathy MM, Kyrychenko A, Battaile KP, Lovell S, Ladokhin AS Toxins (Basel). 2020 Nov 7;12(11). pii: toxins12110704. doi:, 10.3390/toxins12110704. PMID:33171806<ref>PMID:33171806</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7k7d" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Lovell | *[[Diphtheria toxin|Diphtheria toxin]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Battaile KP]] | |||
[[Category: Kashipathy MM]] | |||
[[Category: Ladokhin AS]] | |||
[[Category: Lovell S]] | |||
[[Category: Rodnin MV]] | |||