Dynamics of ATP-binding cassette contribute to allosteric control, nucleotide binding and energy transduction in ABC transporters.
ATP-binding cassette (ABC) transporters move solutes across membranes and are associated with important diseases, including cystic fibrosis and multi-drug resistance. These molecular machines are energized by their charateristic ABC modules, molecular engines fuelled by ATP hydrolysis. A solution NMR study of a model ABC, Methanococcus jannaschii protein MJ1267, reveals that ADP-Mg binding alters the flexibilities of key ABC motifs and induces allosteric changes in conformational dynamics in the LivG insert, over 30A away from the ATPase active site. (15)N spin relaxation data support a "selected-fit" model for nucleotide binding. Transitions between rigidity and flexibility in key motifs during the ATP hydrolysis cycle may be crucial to mechanochemical energy transduction in ABC transporters. The restriction of correlated protein motions is likely a central mechanism for allosteric communications. Comparison between dynamics data from NMR and X-ray crystallography reveals their overall consistency and complementarity.
Department of Biochemistry and Molecular Biophysics, Columbia University, 630 W. 168th St, New York, NY 10032, USA.
Chunyu
C
Wang
Nathan
N
Karpowich
John F
JF
Hunt
Mark
M
Rance
Arthur G
AG
Palmer
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000494:Allosteric Regulation / Q000502:physiology; D018360:Crystallography, X-Ray; D004735:Energy Transfer / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D017017:Methanococcus / Q000378:metabolism; D017434:Protein Structure, Tertiary
D018528:ATP-Binding Cassette Transporters; D000244:Adenosine Diphosphate