[3dem] Free CryoEM Webinar - October 12pm (Eastern)

[Kjirsten Wheeler]

Hello Interested Researchers,



Mark your calendars and register for our next NIH sponsored Joint CryoEM Service Centers Webinar Series “A belt-buckle checkpoint sets the onset of BoNT intoxication: from structure to rational design” by Dr. Linfeng (Daniel) Gao from the University of California, Irvine will be next Thursday, October 29th, at 12pm (Eastern Time) (see attachment or below for details).



Registration is at no-cost, but sign-up is required: <zoom link>



For more information regarding the National CryoEM Service Centers can be found at https://urldefense.com/v3/__https://www.cryoemcenters.org/cryoem-centers/__;!!Mih3wA!GH4ZtEnFQUgORkQe9uWTwuJsiaj4H9rYptcqagMNVmRnzLk-Rt7Mju8MQgYDgOtnZB34c1ndIZ2yTShnoGTa$ .



Best,

(Include the PDF flyer and a text version in the body of the email)

_________________________
Kjirsten Wheeler
PNCC Program Administrator

Pacific Northwest Cryo-EM Center
a PNNL and OHSU affiliation Website<https://urldefense.com/v3/__https:/pncc.labworks.org/__;!!Mi0JBg!burdB2N3-jSi-4APwohcbkMgXzrhpmrr-Q_XadX2I6g6qfUKLs-MOS_CSrl8z8tr$>  LinkedIn<https://urldefense.com/v3/__https://ohsuitg.sharepoint.com/sites/PROJ.PNCC/Shared*20Documents/General/PNCC_Workshops*20&*20Training/SerialEM*20Screening*20Workshop/pacific-northwest-cryo-em-center__;JSUlJSU!!Mih3wA!GH4ZtEnFQUgORkQe9uWTwuJsiaj4H9rYptcqagMNVmRnzLk-Rt7Mju8MQgYDgOtnZB34c1ndIZ2yTTMySrrd$ >  YouTube<https://urldefense.com/v3/__https://www.youtube.com/@pacificnorthwestcryoemcenter/videos__;!!Mih3wA!GH4ZtEnFQUgORkQe9uWTwuJsiaj4H9rYptcqagMNVmRnzLk-Rt7Mju8MQgYDgOtnZB34c1ndIZ2yTZ0qJLvl$ >

wheelekj at ohsu.edu<mailto:wheelekj at ohsu.edu>



CryoEM Current Practices Webinar
A belt-buckle checkpoint sets the onset of BoNT intoxication: from structure to rational design

Dr. Linfeng (Daniel) Gao Assistant Project Scientist,
Department of Physiology & Biophysics
School of Medicine,
University of California, Irvine (UCI)

12PM EDT / 9AM PDT Thursday, October 29, 2026

Fast-acting botulinum neurotoxins (BoNTs) are desirable for treating neurologic conditions requiring rapid intervention and outcome evaluation, and for aesthetic applications seeking quicker results. BoNT/E takes clinical effect 1-day post-injection, much faster than BoNT/A (6-7 days), yet molecular basis for this difference has remained unknown. We demonstrate that the “belt” of BoNTs, a largely unstructured loop wrapping around their catalytic light chain (LC), is key to the onset of intoxication. Cryo-EM analysis of full-length BoNT/E at pH 5, mimicking the endosomal environment, reveals BoNT/E undergoes a conformational transition of a “closed” state at neutral pH to dynamic open conformations at acidic pH, in which the HC domain swings away from a largely rigid LC-HN domain. Loss of HC support renders a large part of the belt segment too flexible to be resolved, demonstrating the BoNT/E belt is intrinsically more flexible than BoNT/A. This flexibility of the BoNT/E belt lowers the energy barrier for LC unfolding and translocation, ultimately contributing to faster onset of BoNT/E action compared to BoNT/A. Furthermore, we identify a regulatory “belt-buckle” checkpoint modulates the release of the belt constraint on the LC. Loosening the belt-buckle of BoNT/A through protein engineering enhances its sensitivity to acidic pH, leading to an accelerated onset of action. Conversely, locking the belt-buckle of BoNT/A via an antibody prevents belt release, thereby neutralizing the toxin. Together, these findings open new avenues for developing fast-acting BoNTs and effective countermeasures.

All are welcome to attend. Registration is at no-cost, but sign-up is required:
https://urldefense.com/v3/__https://us02web.zoom.us/webinar/register/WN_fKZp_OMfSEaLmZwWTa_d9g__;!!Mih3wA!GH4ZtEnFQUgORkQe9uWTwuJsiaj4H9rYptcqagMNVmRnzLk-Rt7Mju8MQgYDgOtnZB34c1ndIZ2yTcn9fW07$ 

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