Journal article
Retinal guanylyl cyclase activating protein 1 forms a functional dimer
PloS one, v 13(3), pp e0193947-e0193947
07 Mar 2018
PMID: 29513743
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Retinal guanylyl cyclases (RetGCs) in vertebrate photoreceptors are regulated by the guanylyl cyclase activator proteins (GCAP1 and GCAP2). Here, we report EPR double electron-electron resonance (DEER) studies on the most ubiquitous GCAP isoform, GCAP1 and site-directed mutagenesis analysis to determine an atomic resolution structural model of a GCAP1 dimer. Nitroxide spin-label probes were introduced at individual GCAP1 residues: T29C, E57C, E133C, and E154C. The intermolecular distance of each spin-label probe (measured by DEER) defined restraints for calculating the GCAP1 dimeric structure by molecular docking. The DEER-derived structural model of the GCAP1 dimer was similar within the experimental error for both the Mg2+-bound activator and Ca2+-bound inhibitor states (RMSD < 2.0 Å). The GCAP1 dimer possesses intermolecular hydrophobic contacts involving the side chain atoms of H19, Y22, F73 and V77. The structural model of the dimer was validated by GCAP1 mutations (H19R, Y22D, F73E, and V77E) at the dimer interface that each abolished protein dimerization. Previous studies have shown that each of these mutants either diminished or completely suppressed the ability of GCAP1 to activate the cyclase. These results suggest that GCAP1 dimerization may affect compartmentalization of GCAP1 in the photoreceptors and/or affect regulation of the cyclase activity.
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Details
- Title
- Retinal guanylyl cyclase activating protein 1 forms a functional dimer
- Creators
- Sunghyuk Lim - University of California, DavisGraham Roseman - University of California, Santa CruzIgor Peshenko - Salus UniversityGrace Manchala - University of California, DavisDiana Cudia - University of California, DavisAlexander M Dizhoor - Salus UniversityGlenn Millhauser - University of California, Santa CruzJames B Ames - University of California, Davis
- Publication Details
- PloS one, v 13(3), pp e0193947-e0193947
- Grant note
- EY012347 / NIH HHS R01 EY012347 / NEI NIH HHS R01 EY011522 / NEI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000426896800092
- Scopus ID
- 2-s2.0-85042939861
- Other Identifier
- 991022035260204721
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- Web of Science research areas
- Biochemistry & Molecular Biology