Sergei Sukharev

About

Sergei Sukharev is a Professor in the Department of Biology at the University of Maryland, with affiliate positions in Chemistry and Biochemistry Graduate Program. He earned his Ph.D. from Moscow State University in 1987, focusing on molecular mechanisms of mechanosensation and mechano-activated ion channels, their structure, and mechanisms of gating by membrane stretch. His research investigates the principles and molecules that cells use to detect mechanical force and pressure, encompassing phenomena from bacterial adaptation to osmotic changes to complex processes such as hearing, balance, and gravitropism in animals and plants. Dr. Sukharev has made significant contributions to the field, notably in the isolation and cloning of the Mechanosensitive Channel of Large conductance of Escherichia coli (MscL), the first identified channel of this class. His work involves interdisciplinary approaches including molecular modeling, genetic modifications, biochemical purification, reconstitution into membranes, single-channel recording, and video imaging. His research addresses the structure and gating mechanisms of mechanosensitive channels, with a focus on understanding how interactions within these proteins keep channels closed at rest and allow them to open under tension. He has received awards such as the J. W. Ritter Award in 1988 and the University of Maryland College of Life Sciences Junior Faculty Award in 2000.

Research topics

• Chemistry
• Biophysics
• Biology
• Materials science
• Cell biology

Selected publications

• Mechanism of Catalysis by <scp>l</scp>-Asparaginase

  Biochemistry · 2020-05-04 · 59 citations

  articleOpen access

  Two bacterial type II l-asparaginases, from Escherichia coli and Dickeya chrysanthemi, have played a critical role for more than 40 years as therapeutic agents against juvenile leukemias and lymphomas. Despite a long history of successful pharmacological applications and the apparent simplicity of the catalytic reaction, controversies still exist regarding major steps of the mechanism. In this report, we provide a detailed description of the reaction catalyzed by E. coli type II l-asparaginase (…

  PublisherOA PDFDOI

• Partitioning of Seven Different Classes of Antibiotics into LPS Monolayers Supports Three Different Permeation Mechanisms through the Outer Bacterial Membrane

  Langmuir · 2021-01-15 · 35 citations

  articleOpen accessSenior authorCorresponding

  The outer membrane (OM) of Gram-negative (G−) bacteria presents a barrier for many classes of antibacterial agents. Lipopolysaccharide (LPS), present in the outer leaflet of the OM, is stabilized by divalent cations and is considered to be the major impediment for antibacterial agent permeation. However, the actual affinities of major antibiotic classes toward LPS have not yet been determined. In the present work, we use Langmuir monolayers formed from E. coli Re and Rd types of LPS to record pr…

  PublisherOA PDFDOI

• A novel mechanosensitive channel controls osmoregulation, differentiation, and infectivity in Trypanosoma cruzi

  eLife · 2021-07-02 · 30 citations

  articleOpen access

  The causative agent of Chagas disease undergoes drastic morphological and biochemical modifications as it passes between hosts and transitions from extracellular to intracellular stages. The osmotic and mechanical aspects of these cellular transformations are not understood. Here we identify and characterize a novel mechanosensitive channel in T rypanosoma cruzi (TcMscS) belonging to the superfamily of small-conductance mechanosensitive channels (MscS). TcMscS is activated by membrane tension an…

  PublisherOA PDFDOI

• MscS inactivation and recovery are slow voltage-dependent processes sensitive to interactions with lipids

  Biophysical Journal · 2023-12-13 · 9 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• The lipid-mediated mechanism of mechanosensitive channel MscS inactivation

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-25 · 6 citations

  preprintOpen accessCorresponding

  MscS is an adaptive osmolyte release valve that regulates turgor in osmotically stressed cells. MscS promptly opens under abrupt super-threshold tensions in the membrane, but at lower and more gradually applied tensions, it silently inactivates from the closed state. A central question has been whether to assign the commonly observed non-conductive conformation with splayed peripheral helices to a closed or inactivated state. We present a 3-Å MscS cryo-EM structure obtained in Glyco-DIBMA polyme…

  PublisherOA PDFDOI

Recent grants

• The bacterial mechanosentitive channel as a multimodal sensor device

  NIH · $1.1M · 2013–2018

• A Comprehensive approach to bacterial osmotolerance

  NIH · $2.2M · 2018–2025

• NIH Grant R01NS039314

  NIH · $2.3M · 2011

Frequent coauthors

• Andriy Anishkin

  University of Maryland, College Park

  83 shared

• Leonid Chernomordik

  Institute of Neuroimmunology of the Slovak Academy of Sciences

  23 shared

• Madolyn Britt

  University of Maryland, College Park

  22 shared

• Elissa Moller

  20 shared

• Vadim A. Klenchin

  University of Wisconsin–Madison

  18 shared

• Uğur Çetiner

  18 shared

• Kishore Kamaraju

  University of Maryland, College Park

  17 shared

• Ian Rowe

  University of Maryland, College Park

  17 shared

Education

• Ph.D., Biology

  Moscow State University

Awards & honors

• J. W. Ritter Award (1988)
• University of Maryland, College of Life Sciences Junior Facu…

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