Conformational changes in guanylate cyclase-activating protein 1 induced by Ca2+ and N-terminal fatty acid acylation.
Neuronal Ca(2+) sensors (NCS) are high-affinity Ca(2+)-binding proteins critical for regulating a vast range of physiological processes. Guanylate cyclase-activating proteins (GCAPs) are members of the NCS family responsible for activating retinal guanylate cyclases (GCs) at low Ca(2+) concentrations, triggering synthesis of cGMP and recovery of photoreceptor cells to the dark-adapted state. Here we use amide hydrogen-deuterium exchange and radiolytic labeling, and molecular dynamics simulations to study conformational changes induced by Ca(2+) and modulated by the N-terminal myristoyl group. Our data on the conformational dynamics of GCAP1 in solution suggest that Ca(2+) stabilizes the protein but induces relatively small changes in the domain structure; however, loss of Ca(+2) mediates a significant global relaxation and movement of N- and C-terminal domains. This model and the previously described "calcium-myristoyl switch" proposed for recoverin indicate significant diversity in conformational changes among these highly homologous NCS proteins with distinct functions.
Orban
Tivadar
T
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4965, USA.
Bereta
Grzegorz
G
Miyagi
Masaru
M
Wang
Benlian
B
Chance
Mark R
MR
Sousa
Marcelo Carlos
MC
Palczewski
Krzysztof
K
D000215:Acylation; D000595:Amino Acid Sequence; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D041961:Deuterium Exchange Measurement; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism*; D051604:Guanylate Cyclase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D005227:Fatty Acids; D051604:Guanylate Cyclase-Activating Proteins; D002118:Calcium