High-pressure NMR study of the complex of a GTPase Rap1A with its effector RalGDS. A conformational switch in RalGDS revealed from non-linear pressure shifts.
Unusually large non-linear 1H and 15N nuclear magnetic resonance chemical shifts against pressure have been detected for individual amide groups of the Ras-binding domain of Ral guanine dissociation stimulator (GDS). The non-linear response is largest in the region of the protein remote from the Rap1A-binding site, which increases by about two-fold by the complex formation with its effector protein Rap1A. The unusual non-linearity is explained by the increasing population of another conformer (N'), lying energetically above the basic native conformer (N), at higher pressure. It is considered likely that the conformational change from N to N' in the Ras-binding domain of RalGDS works as a switch to transmit the effector signal further to molecules of different RalGDS-dependent signaling pathways.
Inoue
K
K
Graduate School of Science and Technology, Kobe University, Japan.
Maurer
T
T
Yamada
H
H
Herrmann
C
C
Horn
G
G
Kalbitzer
H R
HR
Akasaka
K
K
D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011312:Pressure; D015398:Signal Transduction; D020726:ral Guanine Nucleotide Exchange Factor / Q000737:chemistry*; D020827:rap1 GTP-Binding Proteins / Q000737:chemistry*
D020726:ral Guanine Nucleotide Exchange Factor; D020827:rap1 GTP-Binding Proteins