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PMID: 20152158 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Conformational changes in guanylate cyclase-activating protein 1 induced by Ca2+ and N-terminal fatty acid acylation.

Structure (London, England : 1993) ·Vol. 18 ·No. 1 ·2010-01-13 ·Pages 116-26

Orban T, Bereta G, Miyagi M, Wang B, Chance MR, Sousa MC, Palczewski K

Abstract

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.

MeSH Terms
Acylation Amino Acid Sequence Calcium/chemistry,metabolism Deuterium Exchange Measurement Fatty Acids/chemistry,metabolism Guanylate Cyclase-Activating Proteins/chemistry,metabolism Models, Molecular Molecular Dynamics Simulation Molecular Sequence Data Protein Binding Protein Structure, Tertiary
Chemicals
Fatty Acids Guanylate Cyclase-Activating Proteins Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Orban Tivadar
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4965, USA.
Bereta Grzegorz
Miyagi Masaru
Wang Benlian
Chance Mark R
Sousa Marcelo Carlos
Palczewski Krzysztof
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
1878-4186
DOI
10.1016/j.str.2009.11.008
Published
2010-01-13
Pages
116-26
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC2822722
Subset
IM
Grants
NEI NIH HHS · R01 EY009339 · United States
NEI NIH HHS · EY 01979 · United States
NEI NIH HHS · EY 019478 · United States
NEI NIH HHS · R01 EY019050-02 · United States
NIBIB NIH HHS · EB 9998 · United States
NEI NIH HHS · R01 EY019050 · United States
NIBIB NIH HHS · P30 EB009998 · United States
NEI NIH HHS · R01 EY009339-20S1 · United States
NIBIB NIH HHS · P41 EB001979 · United States
NEI NIH HHS · R01 EY019050-03 · United States
NEI NIH HHS · R01 EY019050-01A1 · United States
NEI NIH HHS · EY 019050 · United States
NEI NIH HHS · EY 008061 · United States
External Links
PubMed source DOI: 10.1016/j.str.2009.11.008 PMC Full Text View journal details
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