Calcium binding, structural stability and guanylate cyclase activation in GCAP1 variants associated with human cone dystrophy

  • Dell'Orco, Daniele
  • Behnen, Petra
  • Linse, Sara
  • Koch, Karl-Wilhelm
Publication date
January 2010
Publisher
Springer Science and Business Media LLC

Abstract

Guanylate cyclase activating protein 1 (GCAP1) is a neuronal Ca2+ sensor (NCS) that regulates the activation of rod outer segment guanylate cyclases (ROS-GCs) in photoreceptors. In this study, we investigated the Ca2+-induced effects on the conformation and the thermal stability of four GCAP1 variants associated with hereditary human cone dystrophies. Ca2+ binding stabilized the conformation of all the GCAP1 variants independent of myristoylation. The myristoylated wild-type GCAP1 was found to have the highest Ca2+ affinity and thermal stability, whereas all the mutants showed decreased Ca2+ affinity and significantly lower thermal stability in both apo and Ca2+-loaded forms. No apparent cooperativity of Ca2+ binding was detected for any va...

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