Pharmacological Sciences

Structures of Representative Channel and Transporter Proteins

Ph.D., Mayo Graduate School of Medicine, 1996

Channels and transporters are two major classes
of integral membrane proteins that mediate regulated passages of ions and solutes
across biomembranes. Our research focus is to determine structures of representative
channel and transporter proteins in order to elucidate the chemical basis of
transmembrane active processes. X-ray crystallography is the tool of structural
determination, and the cornerstone on which we will build our research program
on two fronts. Theoretically, we will formulate theories to describe dynamics
and energetics of transmembrane movements of ions and solutes. Practically,
we will carry out structure-based drug design targeting disorders of transmembrane
functions. Towards these ends, we are developing a general approach for crystallization
of integral membrane proteins using multidisciplinary techniques of Protein
Chemistry, Molecular biology and Membrane Biophysics.

Dax Fu holds a joint appointment at Brookhaven National Laboratory
(BNL). Click here for his BNL homepage

Selected Publications

• Fu D, Sarker RI, Abe K, Bolton E and Maloney PC, Structure/function relationships in OxlT, the oxalate-formate
  transporter of oxalobacter formigenes. Assignment of transmembrane helix 11
  to the translocation pathway. J. Biol. Chem. 276, 8753-8760 (2001).
• Fu D, Libson A, Miercke LJ, Weitzman
  C, Nollert P, Krucinski J and Stroud RM, Structure of a glycerol-conducting
  channel and the basis for its selectivity. Science 290, 481-486 (2000).
• Fu D and Maloney PC, Structure-function
  relationships in OxlT, the oxalate/formate transporter of Oxalobacter formigenes.
  Topological features of transmembrane helix 11 as visualized by site-directed
  fluorescent labeling. J. Biol. Chem. 273, 17962-17967 (1998).
• Fu D and Maloney PC, Evaluation
  of secondary structure of OxlT, the oxalate transporter of Oxalobacter formigenes,
  by circular dichroism spectroscopy. J. Biol. Chem. 272, 2129-2135 (1997).
• Fu D and Sine SM, Asymmetric contribution
  of the conserved disulfide loop to subunit oligomerization and assembly of the
  nicotinic acetylcholine receptor. J. Biol. Chem. 271, 31479-31484 (1996).
• Fu D and Sine SM, Competitive antagonists
  bridge the alpha-gamma subunit interface of the acetylcholine receptor through
  quaternary ammonium-aromatic interactions. J. Biol. Chem. 269, 26152-26157
  (1994).