Conformational Changes in Guanylate Cyclase-Activating Protein 1 Induced by Ca2+ and N-Terminal Fatty Acid Acylation
Neuronal Ca{sup 2+} sensors (NCS) are high-affinity Ca{sup 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{sup 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{sup 2+} and modulated by the N-terminal myristoyl group. Our data on the conformational dynamics of GCAP1 in solution suggest that Ca{sup 2+} stabilizes the protein but induces relatively small changes in the domain structure; however, loss of Ca{sup 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.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 1020013
- Report Number(s):
- BNL--95859-2011-JA
- Journal Information:
- Structure, Journal Name: Structure Journal Issue: 1 Vol. 18; ISSN 0969-2126
- Country of Publication:
- United States
- Language:
- English
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