Prof. Amy Rosenzweig
Title: Seeing copper enzymes in their native membrane environment
Bio: Amy C. Rosenzweig is the Weinberg Family Distinguished Professor of Life Sciences in the Departments of Molecular Biosciences and Chemistry at Northwestern University. Her research group is focused on understanding metalloprotein function on the molecular level, using interdisciplinary approaches to attack problems at the forefront of bioinorganic chemistry. Rosenzweig’s areas of interest include biological methane oxidation, oxygen activation by metalloenzymes, metal uptake and transport, and natural products biosynthesis. She is widely recognized as the world expert on particulate methane monooxygenase, an integral membrane metalloenzyme that converts methane, the most inert hydrocarbon, to methanol. This reaction has significant implications for catalysis, global warming, and bioremediation. Rosenzweig, a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences, received a B.A. in Chemistry from Amherst College and a Ph.D. in Inorganic Chemistry from Massachusetts Institute of Technology. Her accomplishments have been recognized by the American Chemical Society Alfred Bader Award in Bioinorganic or Bioorganic Chemistry, the Protein Society Hans Neurath Award, the Royal Society of Chemistry Joseph Chatt Award, the American Chemical Society Nobel Laureate Signature Award for Graduate Education, an Honorary Doctor of Science Degree from Amherst College, and a MacArthur Fellowship.
Abstract: Aerobic microbial processes are important sources and sinks for greenhouse gases with methane-oxidizing bacteria (methanotrophs) consuming methane and ammonia-oxidizing bacteria (nitrifiers) releasing nitrous oxide. Methanotrophs and nitrifiers use copper-dependent membrane monooxygenases to carry out the first steps in their metabolisms: the conversions of methane to methanol by particulate methane monooxygenase (pMMO) and ammonia to hydroxylamine by ammonia monooxygenase (AMO). Due to loss of enzymatic activity upon detergent solubilization from their native intracytoplasmic membranes (ICMs), elucidating the structures and mechanisms of pMMO and AMO has posed significant challenges. Both enzymes consist of three subunits, including PmoB/AmoB, PmoA/AmoA, and PmoC/AmoC. Despite the availability of multiple crystal and cryoelectron microscopy (cryoEM) structures, the location and nature of the pMMO copper active site remain controversial. Attempts to study AMO have not been successful, leaving details of its molecular architecture and copper centers unknown. Using cryoEM single particle analysis, we have visualized both pMMO and AMO directly in their native ICMs at high resolution. These in situ structures reveal the arrangement of enzyme trimers in the membrane, details of the copper centers, bound lipids, and previously unobserved components. The ability to obtain molecular level insight within the native environment will enable further understanding of these and other environmentally-important membrane-bound cuproenzymes.
Keywords: Methane oxidation, metalloenzyme, copper, membrane protein, cryoEM
Host: Prof. Monica Neugebauer