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Revealing
the atomic basis of ion transport Ion channels
are integral membrane proteins that catalyze the diffusion of ions across the
cell membrane. The function of ion channels underlies many essential biological
processes such as muscle contraction and generation of electrical signals in the
nervous system. There are two central questions in the study of ion channels:
how ions permeate the pore, and how the pore opens and closes (gates) in response
to a specific stimulus. In my laboratory, we study these questions using a combined
approach of X-ray crystallography and electrophysiology. Currently, we are focusing
on the sturdy of the cation channels from the transient receptor potential (TRP)
super-family. In addition, we also study how some small molecules - ion channel
blockers - can affect ion permeation of potassium channels. Understanding the
interactions between channels and their blockers would provide valuable information
for drug design. Recent publications: Zhou
Y., MacKinnon R. Ion
binding affinity in the cavity of the KcsA potassium channel. Biochemistry
2004 May 4;43(17):4978-82. Zhou
Y., MacKinnon R. The
occupancy of ions in the K+ selectivity filter: charge balance and coupling of
ion binding to a protein conformational change underlie high conduction rates.
J Mol Biol. 2003 Nov 7; 333(5):965-75.
Valiyaveetil F.I., Zhou Y., MacKinnon R. Lipids
in the structure, folding, and function of the KcsA K+ channel. Biochemistry
2002 Sep 3; 41(35): 10771-7. Zhou,
Y., Morais-Cabral, JH., Kaufman, A., MacKinnon, R., Chemistry
of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0
A resolution. Nature. 2001 Nov 1; 414(6859):43-8. Morais-Cabral,
JH., Zhou, Y., MacKinnon, R. Energetic
optimization of ion conduction rate by the K+ selectivity filter. Nature 2001
Nov 1; 414: 37-42.
yufeng.zhou@yale.edu |  |