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Calcium binding, st...
Calcium binding, structural stability and guanylate cyclase activation in GCAP1 variants associated with human cone dystrophy
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Dell'Orco, Daniele (author)
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Behnen, Petra (author)
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- Linse, Sara (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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Koch, Karl-Wilhelm (author)
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(creator_code:org_t)
- 2010-01-07
- 2010
- English.
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In: Cellular and Molecular Life Sciences. - : Springer Science and Business Media LLC. - 1420-9071 .- 1420-682X. ; 67:6, s. 973-984
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Photoreceptor
- Neuronal calcium sensor
- GCAP
- Cone dystrophy
Publication and Content Type
- art (subject category)
- ref (subject category)
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