Dr. Sharon Ruthstein

Dr. Sharon Ruthstein


Protein structure and function, structural biology, magnetic resonance, metalloproteins.


More than 30% of all proteins in the cell exploit one or more metals to perform their specific functions, and over 40% of all enzymes contain metals. Metals are commonly found as natural constituents of proteins; however, many metal ions can be toxic when free in biological fluids. Hence, the human bodies as well as microorganisms have evolved considerable regulatory machinery to acquire, utilize, traffic, detoxify, and otherwise manage the intracellular and extracellular concentrations and types of metal ions. Despite the high regulation of metal ions in the human body, diseases such as Menkes, Wilson, Alzheimer’s, Parkinson’s and Prion’s have been linked with metal binding to proteins.

Dr. Ruthstein’s lab will look into some of the significant and least understood biological processes that are related to metal ion transportation and intracellular distribution, as well as unwanted processes due to high metal concentration or protein mutations. The aims are:

(i)     To obtain structural information on intrinsically disordered N-terminal domain in metal transporters, in order to understand metal ion transportation to the cells.

(ii)   To understand the metal binding mechanism of metal sensors in bacterial cells, in order to shed light on the metal regulatory machinery of the bacteria.

(iii) To explore the copper transport and distribution mechanisms in human cells, in order to get to the core of the copper homeostasis mechanism.

(iv) To characterize the role of copper and mutations on the aggregation and folding of proteins, in order to illuminate the microscopic origins of neurological diseases.


To comprehend such processes it is necessary to be sensitive to the structural changes that occur in the protein upon metal binding. The main biophysical tool that is used in the lab of Dr. Ruthstein’s lab is pulsed EPR spectroscopy. The power of EPR lies in the sensitivity to both atomic level changes and nanoscale fluctuations. EPR can characterize properties such as redox state and ligand geometry for different functional states of the protein. In addition, EPR can measure distances between paramagnetic probes up to 80 Å