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UID:512@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20140106T130000

DTEND;TZID=Asia/Jerusalem:20140106T140000

DTSTAMP:20210802T125834Z

URL:https://biology.technion.ac.il/en/seminars/dr-yoni-haitin-department-o
 f-physiology-and-biophysics-university-of-washington-seattle-2/

SUMMARY:Dr. Yoni Haitin\, Department of Physiology and Biophysics\, Univers
 ity of Washington\, Seattle. [No Categories]
DESCRIPTION:Location:   \n Affiliation: \n Host:\n "KCNH Channel Regulation
 : A Structural Point of View"\nAbstract:\nThe KCNH voltage dependent potas
 sium channels are key regulators of cellular excitability\, involved in ca
 rdiac long QT syndrome type 2 (LQTS2)\, epilepsy\, schizophrenia and cance
 r. The intracellular domains of KCNH channels are structurally distinct fr
 om other voltage-gated channels\, and include an amino-terminal eag domain
 \, composed from a Per-Arnt-Sim (PAS) module and a PAS-cap region\, and a 
 carboxy-terminal cyclic nucleotide-binding homology domain (CNBHD)\, conne
 cted to the pore domain through a C-linker domain. These specialized intra
 cellular domains are the site of many disease-causing mutations and bestow
  unique gating and regulation on KCNH channels. Using fluorescence\, x-ray
  crystallography and electrophysiological approaches\, we determined and v
 alidated the structure of the intracellular complex of mEAG1 channel. Harb
 oring many LQTS2 and cancer-associated mutations\, the eag domain-CNBHD in
 terface involves three important regions: (i) the “intrinsic ligand” m
 otif\, a unique structural feature of the CNBHD\; (ii) the post-CNBHD regi
 on\, known to mediate EAG channels regulation by a variety of cellular sig
 naling events\; and finally\, (iii) the PAS-cap region\, which constitutes
  the first 25 amino acids of the eag domain\, and forms a highly conserved
  amphipathic helix (αCAP). Together\, this work provides a detailed physi
 ological and pathophysiological description of the intracellular domain of
  the KCNH family.\nמארחת: פרופ"ח פיליפה מלמד\n 

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