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SUMMARY:Keynote 10\, Prof Erik Lindahl: Deciphering Allosteric Modulation 
 in Ligand-Gated Ion Channels with Simulations\, X-ray crystallography\, Cr
 yo-EM and Neutron Scattering
DTSTART;VALUE=DATE-TIME:20191011T091000Z
DTEND;VALUE=DATE-TIME:20191011T095000Z
DTSTAMP;VALUE=DATE-TIME:20260525T074319Z
UID:indico-contribution-143-774@lindico453.srv.lu.se
DESCRIPTION:Speakers: Erik Lindahl (Stockholm University)\nLigand-gated io
 n channels control the electrical excitation of nerve cells\, in particula
 r in the post-synaptic membrane in response to chemical signals mediated b
 y neurotransmitters. These receptors exhibit an amazing diversity in detai
 led structure and function - some human channels have 15-20 slightly genes
 \, and with five subunits this can theoretically lead to almost a million 
 different oligomers. They are further characterised by adopting both close
 d\, open and desensitised states - and in addition to the neurotransmitter
 s causing normal opening they are subject to secondary control - allosteri
 c modulation - by a number of drugs such as alcohols\, benzodiazepines\, n
 eurosteroids\, and anaesthetics that either potentiate or inhibit the agon
 ist response. I will present our work on understanding the molecular mecha
 nisms of these channels by using a broad range of experimental and theoret
 ical methods\, and illustrate that while each method has many shortcomings
  their combination increasingly enable us to capture different timescales\
 , features\, interactions and not least dynamics of important membrane pro
 teins. For ligand-gated ion channels in particular\, this has enabled us t
 o explain several key mechanisms\, including identifying the separate pote
 ntiating and inhibitory binding sites\, showing how we can reverse the all
 osteric modulation of specific channels\, and propose detailed functional 
 models even from intermediate-resolution structural data.\n\nhttps://lindi
 co453.srv.lu.se/event/125/contributions/774/
LOCATION:Kulturen Auditorium
URL:https://lindico453.srv.lu.se/event/125/contributions/774/
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SUMMARY:Short Talk 12\, Magnus Andersson - Tracking Ca2+ ATPase Intermedia
 tes in Real-Time by X-ray Solution Scattering
DTSTART;VALUE=DATE-TIME:20191011T085000Z
DTEND;VALUE=DATE-TIME:20191011T091000Z
DTSTAMP;VALUE=DATE-TIME:20260525T074319Z
UID:indico-contribution-143-773@lindico453.srv.lu.se
DESCRIPTION:Speakers: Magnus Andersson (Umeå University)\nSarco/endoplasm
 ic reticulum Ca2+ ATPase (SERCA) transporters regulate calcium signaling b
 y active calcium\nion reuptake to internal stores. Several of the structur
 al transitions associated with transport have been characterized\nby X-ray
  crystallography\, but critical intermediates of the inward-outward switch
 ing are missing.\nWe combined time-resolved X-ray solution scattering (TR-
 XSS) experiments and molecular dynamics (MD)\nsimulations for real-time tr
 acking of concerted SERCA reaction-cycle dynamics in the native membrane. 
 The\nTR-XSS pre-pulse model differed in the domain arrangement compared to
  Ca2E1 crystal structures. A 1.5\nms intermediate showed closure of the cy
 tosolic domains typical of Ca2+- and ATP-bound E1 states. A subsequent\ntr
 ansi-ent state with a 13 ms rise-time showed a novel actuator (A) domain a
 rrangement that exposes the\nADP-binding site after phosphorylation. Hence
 \, the obtained TR-XSS models determine the relative timing\nof so-far elu
 sive domain rearrangements in a native environment.\n\nhttps://lindico453.
 srv.lu.se/event/125/contributions/773/
LOCATION:Kulturen Auditorium
URL:https://lindico453.srv.lu.se/event/125/contributions/773/
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