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Calcium binding, st...
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Dell'Orco, Daniele
(författare)
Calcium binding, structural stability and guanylate cyclase activation in GCAP1 variants associated with human cone dystrophy
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
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2010-01-07
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Springer Science and Business Media LLC,2010
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:8ca325e6-3098-4228-9ece-c80af35e2671
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https://lup.lub.lu.se/record/1568311URI
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https://doi.org/10.1007/s00018-009-0243-8DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Behnen, Petra
(författare)
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Linse, SaraLund 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(Swepub:lu)fkm2-sli
(författare)
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Koch, Karl-Wilhelm
(författare)
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Biokemi och StrukturbiologiCentrum för Molekylär Proteinvetenskap
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cellular and Molecular Life Sciences: Springer Science and Business Media LLC67:6, s. 973-9841420-90711420-682X
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