1 H N, 13 C, and 15 N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A tran
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ARTICLE
1 N, 13
H C, and 15N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2) Kristen M. Varney1 · Paul T. Wilder1 · Raquel Godoy‑Ruiz1 · Filippo Mancia2 · David J. Weber1 Received: 13 February 2019 / Accepted: 8 March 2019 © Springer Nature B.V. 2019
Abstract Vitamin A is a necessary nutrient for all mammals, and it is required for the transcription of many genes and vital for vision. While fasting, the vitamin A alcohol form (Retinol) from storage in the liver is mobilized and transported through the bloodstream while bound to retinol binding protein (RBP). Details of how exactly vitamin A is released from RBP and taken into the cells are still unclear. As part of the effort to elucidate the specifics of this process, single-particle cryo-electron microscopy structural studies of STRA6 (the RBP receptor 75-kDa transmembrane receptor protein) were recently reported by Chen et al. (Science, https://doi.org/10.1126/science.aad8266, 2016). Interestingly, STRA6 from zebrafish was shown to be a stable dimer and bound to calmodulin (CaM), forming a 180-kDa complex. The topology of the STRA6 complex includes 18 transmembrane helices (nine per protomer) and two long horizontal intramembrane helices interacting at the dimer core (Chen et al., in Science, https://doi.org/10.1126/science.aad8266, 2016). CaM was shown to interact with three regions of STRA6, termed CaMBP1, CaMBP2, and CaMBP3, with the most extensive interactions involving CaMBP2. To further our understanding of C a2+-dependence of CaM-STRA6 complex formation, studies of the structure and dynamic properties of the CaMBP2–CaM complex were initiated. For this, the 1HN, 13C, and 15N backbone resonance assignments of the 148 amino acid Ca2+-bound calmodulin protein bound to the 27-residue CaMBP2 peptide derived from STRA6 were completed here using heteronuclear multidimensional NMR spectroscopy. Keywords Vitamin A · Retinoic acid · Calmodulin · STRA6
Biological context Vitamin A is required both for vision and to activate transcription via nuclear receptors such as the retinoic acid receptor (RAR) and the retinoid X receptor (RXR) (Chen et al. 2016; Palczewski 2012; Al Tanoury et al. 2013). Due to its involvement in diverse biological processes, disorders in vitamin A-dependent pathways result in disease states, including blindness and cancer (Shirakami et al. 2012; di Masi et al. 2015). Although a detailed mechanism for vitamin A transport is not fully elucidated, its cellular transport * Kristen M. Varney [email protected] 1
Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics (CBT), University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD 21201, USA
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA
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channel, STRA6, was proved necessary. STRA6 was shown to promote the release of retinol from the retinol binding protein (RBP), which transports and protects vitamin A i
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