Confirming the revised C-terminal domain of the MscL crystal structure.
The structure of the C-terminal domain of the mechanosensitive channel of large conductance (MscL) has generated significant controversy. As a result, several structures have been proposed for this region: the original crystal structure (1MSL) of the Mycobacterium tuberculosis homolog (Tb), a model of the Escherichia coli homolog, and, most recently, a revised crystal structure of Tb-MscL (2OAR). To understand which of these structures represents a physiological conformation, we measured the impact of mutations to the C-terminal domain on the thermal stability of Tb-MscL using circular dichroism and performed molecular dynamics simulations of the original and the revised crystal structures of Tb-MscL. Our results imply that this region is helical and adopts an alpha-helical bundle conformation similar to that observed in the E. coli MscL model and the revised Tb-MscL crystal structure.
Maurer
Joshua A
JA
Department of Chemistry, Washington University, St. Louis, Missouri 63130, USA. maurer@wustl.edu
Elmore
Donald E
DE
Clayton
Daniel
D
Xiong
Li
L
Lester
Henry A
HA
Dougherty
Dennis A
DA
D003198:Computer Simulation; D003461:Crystallography / Q000379:methods; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D007473:Ion Channels / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli