A large iris-like expansion of a mechanosensitive channel protein induced by membrane tension.
MscL, a bacterial mechanosensitive channel of large conductance, is the first structurally characterized mechanosensor protein. Molecular models of its gating mechanisms are tested here. Disulfide crosslinking shows that M1 transmembrane alpha-helices in MscL of resting Escherichia coli are arranged similarly to those in the crystal structure of MscL from Mycobacterium tuberculosis. An expanded conformation was trapped in osmotically shocked cells by the specific bridging between Cys 20 and Cys 36 of adjacent M1 helices. These bridges stabilized the open channel. Disulfide bonds engineered between the M1 and M2 helices of adjacent subunits (Cys 32-Cys 81) do not prevent channel gating. These findings support gating models in which interactions between M1 and M2 of adjacent subunits remain unaltered while their tilts simultaneously increase. The MscL barrel, therefore, undergoes a large concerted iris-like expansion and flattening when perturbed by membrane tension.
Betanzos
Monica
M
Department of Biology, University of Maryland, College Park, Maryland 20742, USA.
Chiang
Chien-Sung
CS
Guy
H Robert
HR
Sukharev
Sergei
S
D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D016296:Mutagenesis; D018408:Patch-Clamp Techniques; D011487:Protein Conformation
D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli
NASA Discipline Cell Biology; Non-NASA Center