Structural insights into gating mechanism of ion channel proteins and …

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  • Writer 최고관리자
  • 2018-11-15


[Life Sciences / IBB Faculty Candidate Seminar]

 ▶Speaker:  Chanhyung Bae, Ph.D. (Postdoctoral Fellow, National Institutes of Health)

▶Date: 4:00PM/Nov. 19(Mon.)/ 2018

▶Place: Auditorium(1F), Postech Biotech Center

A wide range of physiological processes including the perception of external stimuli, transmission of signals and release of  hormones  depends  upon  the  activity  of  ion  channels,  integral  membrane  proteins  which  selectively  control  the permeation  of  ions  across  cellular  membrane.  Disrupting  the  regulatory  function  of  theses  ion  channels  can  cause adverse consequences in nerves and neuromuscular junctions. As a result, ion channels are frequently the target of peptide toxins produced by venomous creatures, and in this talk I will describe how we can use these toxins to learn about ion channel function and structure.
The first toxin I will discuss is the double-knot toxin (DkTx) from the venom of Chinese bird spider, which binds to and activates  the  transient  receptor  potential  vanilloid  1  (TRPV1)  channel,  a  non-selective  cation  channel  expressed  by sensory neurons which perceive noxious stimuli including heat, inflammation and acidosis. DkTx has an unusual bivalent structure  in  which  two  structurally  similar  domains  (K1  and  K2)  are  joined  by  a  short  linker.  Using  solution  NMR spectroscopy, electrophysiology, molecular dynamics simulations and fluorescence spectroscopy experiments, I found that although the K1 and K2 domains are structurally similar, they evolved for distinct functions with K1 and K2 tuned for membrane partitioning and TRPV1 activation, respectively. In addition, the DkTx/TRPV1 channel complex structure revealed the toxin modulates interactions at the aqueous-membrane interface of a cluster of hydrophobic residues in the pore domain, a region later found to contribute to sensing temperature.
My  second  example  concerns  the  voltage-activated  potassium  (Kv)  channels  expressed  in  excitable  cells  such  as neurons and muscle cells.  Kv  channels  control  membrane voltage by  permeating  potassium  ions  through  the pore domain  of  the  channel  upon  activation  and  by  closing  the  pore  domain  through  inactivation  mechanism,  whose structural  basis  remains unclear.  I will  present a 3.3  Å  resolution  single-particle cryo-electron  microscopy  (cryo-EM) structure of Kv1.2 channel in lipid nanodisc, which provides the glimpse of slow inactivated structure of Kv channels in lipid  membranes,  involving  subtle  structural  changes  in  the  outer  pore  region.  Finally,  I  will  present  unpublished biochemical  results  demonstrating  the  interaction  between  the  Kv  channel  in  nanodisc  and  peptide  toxins  that modulate key domains of the channel. Cryo-EM specimens prepared using the Kv channel and toxins will be imaged to solve the toxin/Kv channel complex structure, which will elucidate the structural basis for inhibition mechanism of the toxins and the structure of Kv channel in different conformations.

▶Contact: Department of Life Sciences (Tel. 279-2721)

* This seminar will be given in English.
please refrain from taking photos during seminars. *