John H. Laity
Associate Professor, CBB
Ph.D. Cornell University
Office: 114 SCB
Phone: (816) 235-5345
E-mail: LaityJ
Laboratory Web Site
Research Areas
Molecular mechanisms of cellular signaling and biomolecular recognition using Nuclear magnetic resonance spectroscopy (NMR), biophysical chemistry and molecular biology. Specific interests include mechanisms that control divalent zinc homeostasis in yeast and mammalian cells.
Current Interests
"We are a new lab using NMR to identify and characterize the molecular mechanisms that control divalent zinc [Zn(II)] homeostasis in yeast and mammalian cells. NMR is a well-suited technique to investigate structural and dynamic changes of proteins in solution. All known organisms require Zn(II), and yet this essential nutrient is toxic if accumulated to excess. Zn(II) homeostasis in mammalian and yeast cells is regulated at least in part at the level of coordination chemistry by two zinc finger proteins, Zap1 (yeast) and MTF-1 (mammalian). MTF-1 and Zap1 are transcription factors that control the expression of proteins to transport Zn(II) in or out of the cellular compartments [Zn(II) transport proteins] or to sequester Zn(II) through high-affinity metal-ligand coordination (metallothioneins). Although both of these Zn(II)-sensing transcription factors respond to changing intracellular Zn(II) levels, Zap1 transcriptional activity is inhibited in an intracellular environment of excess Zn(II), while that of MTF-1 is induced by zinc excess. Clearly, the molecular principles that govern the Zn(II)-dependent changes in transcriptional activity of Zap1 and MTF-1 are distinct. The MTF-1 proteins are the only known sub-group of the large class of DNA-binding zinc finger proteins whose biological function is regulated at the level of Zn(II) coordination to the consensus Cys2His2 structural sites within the protein. "
"Our initial focus involves using two-dimensional NMR experiments to identify the Zn(II) responsive regions of MTF-1 and Zap1. Subsequent in-depth structural and dynamic NMR studies will target the specific molecular interactions governing Zn(II)-induced transcription by these proteins, which may involve interactions between the Zn(II) sensing proteins and cognate DNA promoter sites."
