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Volume 10, Issue 8 (Suppl)
J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
Structural Biology 2017
September 18- 20, 2017
Page 90
conference
series
.com
9
th
International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
Qiu-Xing Jiang, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100
Structural basis for the lipid-dependent gating of a Kv channel
H
uman cell membranes are made of both phospholipids and nonphospholipids. The nonphospholipids, such as cholesterol,
have no phosphate groups in their headgroup regions and are quite abundant in cell membranes. Mainly due to technical
difficulties, quantitative study of possible effects of nonphospholipids on voltage-gated ion channels has been very challenging.
Our prior studies have achieved three major developments: 1. a working hypothesis of lipid-dependent gating based on
nonphospholipids stabilizing the voltage sensor domain of the KvAP channel in the resting (down) conformation, 2. a novel
bead-supported unilamellar membrane system and a new method to stabilize the KvAP channel in the resting state and 3.
chemically functionalized carbon films for cryoEM imaging of low abundance complexes by high-affinity selection or of small
macromolecular complexes (100-200 kDa) by keeping vitrified ice thinner than usual. The general idea for lipid dependent
gating is that the annular lipids around a Kv channel change their arrangements in accompany with the conformational changes
of the voltage-sensor domains. Our technical development made it feasible to study the CHOL-dependent gating effects on Kv
channels. We studied the CHOL-dependent gating effects on Kv channels in bSUMs. Because almost all known lipid metabolic
defects result from dysregulated homeostasis of nonphospholipids, our studies in animal models carrying CHOL metabolic
defects will provide the first test of lipid-dependent gating in an
in vivo
physiological setting. Secondly, we apply our ChemiC
method to cryoEM study of the 120 kDa KvAP in both an inactivated and a peptide-stabilized down state. The peptides selected
from the nonphospholipid-stabilized down state have been showed to recognize the voltage sensors in the right conformation
and keep the channels in the right conformation. Our results will reveal the structural basis for the nonphospholipid-induced
conformational changes in Kv channels, and unveil connections to the lipid-metabolic defects in humans.
Biography
Qiu-Xing Jiang obtained his PhD in 2002 from the Department of Cellular and Molecular Physiology at Yale University School of Medicine, where he started his work in
cryo-electron microscopy in 1999 with Dr. Fred Sigworthis. He is currently heading the Laboratory of Molecular Biophysics and Cell Physiology in Department of Micro-
biology and Cell Science in the Institute of Food and Agricultural Sciences at University of Florida and he is serving part-time (20%) as the Faculty Director of Electron
Microscopy at the Institute of Cross-disciplinary Biotechnology Research at UF. After a short Postdoctoral training at Yale, he finished his Postdoctoral training in structural
biology with Dr. Roderick Mackinnon in 2007 before taking an Assistant Professorship position at UT Southwestern Medical Center at Dallas, Texas. He is the recipient of
the NIH EUREKA award in 2009, the AHA National Innovative Award in 2012, and the Junior Faculty travel award from GRC Molecular and Cell Biology of Lipids in 2011.
qxjiang@ufl.eduQiu-Xing Jiang
University of Florida, USA