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titleboxSERGEI SUKHAREV titlebox

professor pictureAssociate Professor

email:sukharev@umd.edu
phone:
301.405.6923 (office)
301.405.6912 (lab)
301.405.8378
fax:301.314.9358
office:3216 Bio-Psych
graduate programs: Biology, MOCB
bullet visit lab page   bullet most recent publications


RESEARCH INTERESTS

Dr. Sukharev investigates the principles and the molecules that cells use to detect mechanical force and pressure. Mechanosensation encompasses many phenomena from the relatively simple such as bacterial adaptation to osmotic changes in the medium to the very complex such as hearing and balance in animals, or gravitropism in plants; yet many primary receptors responsible for force detection remain unidentified as molecular entities. Mechanosensitive channels that conduct ions across the plasma membrane in response to membrane tension are thought to be primary transducers that convert mechanical stimuli into the form of cellular signals. Dr. Sukharev has made the major effort in isolation and cloning of the Mechanosensitive Channel of Large conductance of Escherichia coli (MscL), the first identified channel of this class. When the closed-state crystal structure of a MscL homolog became available, Dr. Sukharev focused his research on prediction of MscL structure in the open state. His current study addresses the nature of interactions inside the MscL protein that keep the channel firmly closed at rest, but allow it to open under tension of a certain magnitude. The group is also approaching the mechanism of gating of the small bacterial Mechanosensitive Channel, MscS. These interdisciplinary projects involve molecular modeling and simulations, genetic modifications of the channel genes, disulfide cross-linking, biochemical purification of proteins and reconstitution into phospholipid membranes; single-channel recording and video imaging of patch-clamped membranes; kinetic and thermodynamic analysis of the channel behavior.

Recent Publications


Akitake B, Anishkin A, Sukharev S. The "dashpot" mechanism of stretch-dependent gating in MscS. J Gen Physiol. 2005 Feb;125(2):143-54. Epub 2005 Jan 18.
Anishkin A, Chiang CS, Sukharev S. Gain-of-function mutations reveal expanded intermediate states and a sequential action of two gates in MscL. J Gen Physiol. 2005 Feb;125(2):155-70.
Anishkin A, Sukharev S. Explicit channel conductance: can it be computed? Biophys J. 2005 Jun;88(6):3742-3. Epub 2005 Mar 11.
Chiang CS, Shirinian L, Sukharev S. Capping transmembrane helices of MscL with aromatic residues changes channel response to membrane stretch. Biochemistry. 2005 Sep 20;44(37):12589-97.
Anishkin A, Sukharev S, Colombini M. Searching for the molecular arrangement of transmembrane ceramide channels. Biophys J. 2006 Apr 1;90(7):2414-26. Epub 2006 Jan 13.
Akitake B, Spelbrink RE, Anishkin A, Killian JA, de Kruijff B, Sukharev S. 2,2,2-Trifluoroethanol changes the transition kinetics and subunit interactions in the small bacterial mechanosensitive channel MscS. Biophys J. 2007 Apr 15;92(8):2771-84. Epub 2007 Feb 2.
Akitake B, Anishkin A, Liu N, Sukharev S. Straightening and sequential buckling of the pore-lining helices define the gating cycle of MscS.Nat Struct Mol Biol. 2007 Nov 25.
Anishkin A, Akitake B, Sukharev S. Characterization of the resting MscS: modeling and analysis of the closed bacterial mechanosensitive channel of small conductance. Biophys J. 2007 Nov 2.