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Dax Fu

Link to Lab Homepage
Department AffiliationPrimary: Physiology
RankAssociate Professor
Mailing Address725 N. Wolfe Street
Hunterian 401A
Baltimore, MD 21205
Dax Fu Photo

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.

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), in press

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).  PubMed  

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). PubMed

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).  PubMed

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).  PubMed  Full Text

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).  PubMed  Full Text

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).  PubMed  Full Text  PDB file: 2ABM 

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).  PubMed  Full Text

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

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).  PubMed  Full Text

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).  PubMed  Full Text 

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).  PubMed  Full Text  PDB file: 1FX8  

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