Journal article
Structural Basis for Calmodulin as a Dynamic Calcium Sensor
Structure (London), v 20(5), pp 911-923
09 May 2012
PMID: 22579256
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Calmodulin is a prototypical and versatile Ca2+ sensor with EF hands as its high-affinity Ca2+ binding domains. Calmodulin is present in all eukaryotic cells, mediating Ca2+-dependent signaling. Upon binding Ca2+, calmodulin changes its conformation to form complexes with a diverse array of target proteins. Despite a wealth of knowledge on calmodulin, little is known on how target proteins regulate calmodulin's ability to bind Ca2+. Here, we take advantage of two splice variants of SK2 channels, which are activated by Ca2+-bound calmodulin but show different sensitivity to Ca2+ for their activation. Protein crystal structures and other experiments show that, depending on which SK2 splice variant it binds to, calmodulin adopts drastically different conformations with different affinities for Ca2+ at its C-lobe. Such target protein-induced conformational changes make calmodulin a dynamic Ca2+ sensor capable of responding to different Ca2+ concentrations in cellular Ca2+ signaling.
► We show structure of CaM-CaMBD2-b, a SK2 splice variant with reduced Ca2+ sensitivity ► Dramatic changes in the CaM structure in CaM-CaMBD2-b compared to CaM in CaM-CaMBD2-a ► Conformational changes at the CaM C-lobe result in its reduced affinity for Ca2+ ► Results demonstrate CaM alters its affinity for Ca2+ induced by the target proteins
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Details
- Title
- Structural Basis for Calmodulin as a Dynamic Calcium Sensor
- Creators
- Miao Zhang - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USACameron Abrams - Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA 19104, USALiping Wang - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USAAnthony Gizzi - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USALiping He - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USARuihe Lin - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USAYuan Chen - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USAPatrick J Loll - Department of Biochemistry and Molecular Biology, College of Medicine, Drexel University, Philadelphia, PA 19102, USAJohn M Pascal - Department of Biochemistry, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USAJi-fang Zhang - Department of Molecular Physiology and Biophysics, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USA
- Publication Details
- Structure (London), v 20(5), pp 911-923
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Chemical and Biological Engineering
- Web of Science ID
- WOS:000304214400016
- Scopus ID
- 2-s2.0-84861045290
- Other Identifier
- 991014877960804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology