Three routes to modulate the pore size of the MscL channel/nanovalve.
MscL is a bacterial mechanosensitive channel that protects cells from lysis upon acute decrease in external osmotic environment. It is one of the best characterized mechanosensors known, thus serving as a paradigm of how such molecules sense and respond to stimuli. In addition, the fact that it can be genetically modified, expressed, isolated, and manipulated has led to its proposed use as a triggered nanovalve for various functions including sensors within microelectronic array chips, as well as vesicular-based targeted drug release. X-ray crystallography reveals a homopentameric complex with each subunit containing two transmembrane α-helices (TM1 and TM2) and a single carboxyl terminal α-helix arranging within the complex to form a 5-fold cytoplasmic bundle (CB), whose function and stability remain unclear. In this study, we show three routes that throttle the open channel conductance. When the linker between the TM2 and CB domain is shortened by deletions or constrained by either cross-linking or heavy metal coordination, the conductance of the channel is reduced; in the later two cases, even reversibly. While they have implications for the stability of the CB, these data also provide routes for engineering MscL sensors that are more versatile for potential nanotech devices.
Department of Physiology, University of Texas Medical Center at Dallas, Dallas, Texas, United States.
Li-Min
LM
Yang
Robin
R
Wray
Juandell
J
Parker
Danyell
D
Wilson
Randolph S
RS
Duran
Paul
P
Blount
D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019216:Metals, Heavy / Q000378:metabolism; D008958:Models, Molecular; D036103:Nanotechnology / Q000295:instrumentation*; D016062:Porosity; D015202:Protein Engineering / Q000379:methods*; D017433:Protein Structure, Secondary
D029968:Escherichia coli Proteins; D007473:Ion Channels; D019216:Metals, Heavy; C086596:MscL protein, E coli