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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 variant. Finally, the nonmyristoylated mutants were still capable of activating ROS-GC1, but the measured cyclase activity was shifted toward high, nonphysiological Ca2+ concentrations. Thus, we conclude that distorted Ca2+-sensor properties could lead to cone dysfunction.

Detaljer

Författare
  • Daniele Dell'Orco
  • Petra Behnen
  • Sara Linse
  • Karl-Wilhelm Koch
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cellbiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)973-984
TidskriftCellular and Molecular Life Sciences
Volym67
Utgivningsnummer6
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa