Dax Fu

Image of Dr. Dax Fu

Dax Fu

Associate Professor
Primary Appointment: 

725 N. Wolfe Street
Hunterian 401A
Baltimore MD 21205

Research topic: 

Zinc physiology with a focus on structure, function and regulation of zinc transporters

Zinc transporters regulate subcellular zinc distributions to ensure proper metalation of a wide range of cellular proteins that amount to about a third of a mammalian proteome. For example, a human zinc transporter (ZnT8) enriches zinc in the insulin-containing vesicles of pancreatic beta cells where zinc is required for insulin dense core formation. Glucose stimulations trigger zinc and insulin co-secretion. The released zinc serves as an autocrine regulator of insulin secretion and a paracrine regulator of insulin clearance. ZnT8 inhibition could be a potential therapeutic strategy for diabetes. Our research is to understand which step in zinc transport can be modulated and how. The physicochemical principles governing zinc transport have been investigated using an integrated approach of membrane biochemistry, biophysics and structural biology. Parallel cell biology and proteomic approaches are used to understand how these physicochemical principles are applied to mammalian zinc transporters and integrated to physiology of pancreatic beta cells.

Selected Publications: 

Gupta, S, Chai, J., Cheng, J, D'Mello, R, Chance, MC, and Fu, D. Visualizing the kinetic power stroke that drives proton-coupled Zn(II) transport. Nature(2014)

Hoch E, Lin W, Chai J, Hershfinkel M, Fu D, Sekler I. Histidine pairing at the metal transport site of mammalian ZnT transporter controls Zn2+ over Cd2+ selectivity. Proc Natl Acad Sci U.S.A.,109(19):7202-7207 (2012). 

Lin W, Chai J, Love J and Fu D. Selective electrodiffusion of zinc ions in a Zrt-, Irt-like protein, ZIPB. J Biol Chem., 285(50):39013-20 (2010).

Lu M, Chai J and Fu D. Structural basis for autoregulation of the zinc transporter YiiP. Nat. Struct. Mol. Biol., 16(10):1063-1067 (2009).

Lu M and Fu D. Structure of the zinc transport YiiP. Science, 317:1746-8 (2007). PubMed Full Text  See also:Science Perspective by DH Nies: Science 317:1695-1696 (2007).

Fu D and Lu M. The structural basis of water permeation and proton exclusion in aquaporins (Review). Mol Membr Biol., 24(5):366-374 (2007).

Wei Y and Fu D. Binding and transport of metal ions at the dimer interface of the Escherichia coli metal transporter YiiP. J Biol Chem., 281(33):23492-23502 (2006).

Jiang J, Daniels BV and Fu D. Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel. J Biol Chem., 281(1):454-460 (2006).  

Wei Y and Fu D. Selective metal binding to a membrane-embedded aspartate in the Escherichia coli metal transporter YiiP (FieF). J Biol Chem., 280(40):33716-33724 (2005).

Wei Y, Li H and Fu D. Oligomeric state of the Escherichia coli metal transporter YiiP. J Biol Chem., 279(38):39251-39259 (2004).

Chao Y and Fu D. Thermodynamic studies of the mechanism of metal binding to the Escherichia coli zinc transporter YiiP. J Biol Chem., 279(17):17173-17180(2004).

Chao Y and Fu D. Kinetic study of the antiport mechanism of an Escherichia coli zinc transporter, ZitB. J Biol Chem., 279(13):12043-12050 (2004).

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).