Changes in biological activity and folding of guanylate cyclase-activating protein 1 as a function of calcium

Biochemistry
M Rudnicka-NawrotKrzysztof Palczewski

Abstract

Guanylate cyclase-activating protein 1 (GCAP1), a photoreceptor-specific Ca2+-binding protein, activates retinal guanylate cyclase 1 (GC1) during the recovery phase of phototransduction. In contrast to other Ca2+-binding proteins from the calmodulin superfamily, the Ca2+-free form of GCAP1 stimulates the effector enzyme. In this study, we analyzed the Ca2+-dependent changes in GCAP1 structure by limited proteolysis and mutagenesis in order to understand the mechanism of Ca2+-sensitive modulation of GC1 activity. The change from a Ca2+-bound to a Ca2+-free form of GCAP1 increased susceptibility of Ca2+-free GCAP1 to proteolysis by trypsin. Sequencing data revealed that in the Ca2+-bound form, only the N-terminus (myristoylated Gly2-Lys9) and C-terminus (171-205 fragment) of GCAP1 are removed by trypsin, while in the Ca2+-free form, GCAP1 is readily degraded to small fragments. Successive inactivation of each of the functional EF loops by site-directed mutagenesis showed that only EF3 and EF4 contribute to a Ca2+-dependent inactivation of GCAP1. GCAP1(E75D,E111D,E155D) mutant did not bind Ca2+ and stimulated GC1 in a [Ca2+]-independent manner. GCAP1 and GCAP2, but not S-100beta, a high [Ca2+]free activator of GC1, competed with t...Continue Reading

References

Jan 1, 1982·Methods in Enzymology·W F Zimmerman, W Godchaux
Sep 15, 1995·The Journal of Biological Chemistry·W A GorczycaK Palczewski
Feb 1, 1996·Trends in Neurosciences·Y Koutalos, K W Yau
Oct 8, 1962·Biochimica Et Biophysica Acta·J P HUMMEL, W J DREYER

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Citations

Mar 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·K PalczewskiJ B Ames
Dec 29, 1998·Protein Science : a Publication of the Protein Society·R E HughesJ B Hurley
Jun 26, 2003·Journal of Molecular Biology·Ivan I SeninKarl Wilhelm Koch
Feb 28, 2002·Nature Neuroscience·Amy LeeWilliam A Catterall
Jan 8, 2000·The Journal of Biological Chemistry·F HaeseleerK Palczewski
Jan 27, 2007·The Journal of Biological Chemistry·Wolfgang BaehrKrzysztof Palczewski
Jun 11, 2008·The Journal of Biological Chemistry·Igor V PeshenkoAlexander M Dizhoor
Sep 10, 2004·European Journal of Biochemistry·Ji-Young HwangKarl-Wilhelm Koch
Mar 19, 2008·Photochemistry and Photobiology·Ricardo StephenMarcelo Carlos Sousa
Mar 26, 2005·Investigative Ophthalmology & Visual Science·Izabela SokalWolfgang Baehr
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·S L Semple-RowlandW Baehr
Aug 9, 2001·Proceedings of the National Academy of Sciences of the United States of America·A MendezJ Chen
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·C L TuckerJ B Hurley
Sep 1, 2004·Biochemical and Biophysical Research Communications·Krzysztof PalczewskiWolfgang Baehr
Apr 22, 2006·Journal of Molecular Biology·Ricardo StephenMarcelo C Sousa
Dec 3, 1999·Methods : a Companion to Methods in Enzymology·A M Dizhoor, J B Hurley
Oct 9, 2002·Neuron·Marie E BurnsDenis A Baylor
Dec 8, 2000·Biochimica Et Biophysica Acta·I SokalK Palczewski
May 18, 2010·Optometry and Vision Science : Official Publication of the American Academy of Optometry·Hans-Juergen GreinMichael Gebhardt
Feb 26, 1999·The Journal of Biological Chemistry·F HaeseleerK Palczewski
Aug 28, 1999·The Journal of Biological Chemistry·E V OlshevskayaA M Dizhoor
Apr 10, 1999·The Journal of Biological Chemistry·E V OlshevskayaA M Dizhoor
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·A E Otto-BrucK Palczewski

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