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Journal article
Structure of Guanylyl Cyclase Activator Protein 1 (GCAP1) Mutant V77E in a Ca2+-free/Mg2+-bound Activator State
The Journal of biological chemistry, v 291(9), pp 4429-4441
26 Feb 2016
PMID: 26703466
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
GCAP1, a member of the neuronal calcium sensor subclass of the calmodulin superfamily, confers Ca2+-sensitive activation of retinal guanylyl cyclase 1 (RetGC1). We present NMR resonance assignments, residual dipolar coupling data, functional analysis, and a structural model of GCAP1 mutant (GCAP1V77E) in the Ca2+-free/Mg2+-bound state. NMR chemical shifts and residual dipolar coupling data reveal Ca2+-dependent differences for residues 170–174. An NMR-derived model of GCAP1V77E contains Mg2+ bound at EF2 and looks similar to Ca2+ saturated GCAP1 (root mean square deviations = 2.0 Å). Ca2+-dependent structural differences occur in the fourth EF-hand (EF4) and adjacent helical region (residues 164–174 called the Ca2+ switch helix). Ca2+-induced shortening of the Ca2+ switch helix changes solvent accessibility of Thr-171 and Leu-174 that affects the domain interface. Although the Ca2+ switch helix is not part of the RetGC1 binding site, insertion of an extra Gly residue between Ser-173 and Leu-174 as well as deletion of Arg-172, Ser-173, or Leu-174 all caused a decrease in Ca2+ binding affinity and abolished RetGC1 activation. We conclude that Ca2+-dependent conformational changes in the Ca2+ switch helix are important for activating RetGC1 and provide further support for a Ca2+-myristoyl tug mechanism.
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Details
- Title
- Structure of Guanylyl Cyclase Activator Protein 1 (GCAP1) Mutant V77E in a Ca2+-free/Mg2+-bound Activator State
- Creators
- Sunghyuk Lim - University of California, DavisIgor V. Peshenko - Salus UniversityElena V. Olshevskaya - Salus UniversityAlexander M. Dizhoor - Salus UniversityJames B. Ames - University of California, Davis
- Publication Details
- The Journal of biological chemistry, v 291(9), pp 4429-4441
- Publisher
- Elsevier Inc
- Number of pages
- 13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000371604600015
- Scopus ID
- 2-s2.0-84964685831
- Other Identifier
- 991022035262304721
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- Web of Science research areas
- Biochemistry & Molecular Biology