College of Liberal Arts & Sciences

Mark L. Richter

Professor
Primary office:
785-864-3334
4031 Haworth Hall
Room 4031


Research: Application of gene engineering, biochemical and biophysical experiments aimed at elucidating the relationship between the structure and biological function of oligomeric proteins.

Teaching Interests

  • Undergraduate and Graduate Biology
  • Undergraduate and Graduate Biochemistry
  • Graduate Physical Biochemistry

Research

ATP synthase Structure and Function

The F1FO-ATP synthase is a tiny molecular rotary motor driven by binding and hydrolysis of ATP in one direction and by trans-membrane proton flux in the other direction. This complex multi-subunit protein generates sufficient torque to propel large (1-2 micrometers) actin filaments through solution with a remarkably high energy conversion efficiency. The photosynthetic ATP synthase of higher plants has several unique properties that separate it from its mitochondrial and bacterial counterparts and that offer unique inroads to examine the mechanism of energy coupling. One such property is the presence of a special regulatory domain in the γ subunit of higher plant species which, via the reversible oxidation/reduction of an intrinsic dithiol that governs an interaction with the inhibitory ε subunit, provides a molecular "switch" mechanism that tightly controls the catalytic activity of the enzyme. The principle goal of the proposed research is to identify the productive binding interactions between the γ and ε subunits, and between these two subunits and the other F1 subunits, that are involved in the molecular "switch" mechanism. The information to be gained from this work is likely to prove seminal in understanding natural processes that have evolved to gate the motor, in identifying the mechanism of elastic coupling between the FO and F1 segments, and in designing gated nanodevices for future industrial and biomedical applications. Ongoing projects involve: protein engineering, folding and ATPase complex assembly; NMR and crystallization studies of subunit structure; single molecule enzyme analysis using atomic force microscopy, fluorescence and dark-field microscopy; and surface patterning for on-chip fabrication of nanodevices to address industrial and biomedical needs.

Other projects

1) Examination of the structure and function of Parkin, an E3 ligase that plays a central role in regulating the dynamic homeostasis of cellular proteins. Mutations in Parkin lead to familial Parkinson's disease, Alzheimer's disease and Huntington's disease although the mechanism that leads to these various degenerative disorders is not understood. A major interest is identifying the cellular signals and processes that lead to proteins becoming target substrates for poly-ubiquitination by Parkin. Studies involve engineering, biophysical measurements and advanced computer modeling of the Parkin protein to elaborate upon the functions of each of its five different domains.

2) Protein engineering and directed evolution studies of enzymes for use in biosensing applications such as measurements of bioactive molecules (glucose, glutamate, lactate, histamine, nicotine etc.) in the brains of freely moving rodents. Studies mainly involve oxidase enzymes that produce an electroactive product, hydrogen peroxide, that allows detection of tiny amounts of the a target ligand using a sensitive electrode biosensor. As the number of oxidase enzymes is limited in nature, directed evolution experiments are performed to enhance the binding specificity and catalytic properties of enzyme scaffolds.

Research Interests

  • Macromolecular structure, function and dynamics
  • Bioenergetics
  • The role of parkin-dependent ubiquitination in neurobiological disorders
  • Fabrication of micro-biosensors for neurological measurements

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