Download or read book NMR Structures of Neuronal Calcium Sensor Proteins CaBP1 and CaBP4 written by Sae Bo Mi Park and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuronal calcium binding proteins (CaBPs, CaBP1-CaBP5) are a subclass of the calmodulin (CaM) superfamily that regulate specific Ca2+ channel targets in the brain and retina. Calcium-binding protein 1 (CaBP1), is a relatively small Ca2+-binding protein (18.7 kDa) that regulates the Ca2+-dependent activity of inositol 1,4,5-triphosphate receptor (InsP3s) and various voltage-gated Ca2+ channels (Ca[v] 1.2, Ca[v]1.3 and Ca[v] 2.1). In the first project of this study, I present the NMR structure of full-length CaBP1 (18.7 kDa) with Ca2+ bound at EF1, EF3, and EF4-hand, calculated by 1250 nuclear overhauser effect (NOE) distance restraints and 70 residual dipolar coupling (RDC) restraints with a root-mean-squared deviation (RMSD) of 0.54 [angstrom] (N-domain) and 0.48 [angstrom] (C-domain). The Ca2+-saturated CaBP1 structure contains two independent domains separated by a flexible central linker. The N-domain structure of CaBP1 contains two EF-hands (EF1 and EF2) both in a closed conformation, and the C-domain contains EF3 and EF4 in the familiar Ca2+-bound open conformation. The N-domain adopts the same closed conformation in the presence or absence of Ca2+ bound at EF1, in contrast to CaM and other Ca2+ sensor proteins that typically undergo a Ca2+-induced closed-to-open transition. In the second project, I performed a structural study on the calcium binding protein 4 (CaBP4), a somewhat larger Ca2+-binding protein (30 kDa), that serves as a critical regulator of L-type voltage gated Ca2+ channels (Cav1.4) in retinal photoreptors. Accoding to isothermal titration calorimetry (ITC) data and NMR spectra, CaBP4 binds to Mg2+ at EF1 and EF3 in the basal resting state of the cell, in which the cytosolic Ca2+ concentration is 100 nM. CaBP4 binds to Ca2+ at EF1, EF3, and EF4 in the activated cell state, in which the cytosolic Ca2+ concentration increases above 1 [mu]M. I solved the NMR structure of the Ca2+ bound activated and truncated form of CaBP4 (residues 100-271), which excludes unstructured N-terminal residues (1-100). A total of 1443 NOE distance restraints and 176 dihedral angles restraints were used to define overall main chain structure of CaBP4 with RMSD of 0.54 [angstrom] (N-domain) and 0.48 [angstrom] (C-domain). CaBP4 contains two independent domains (N-domain and C-domain) separated by a flexible central linker similar to those of CaBP1, calmodulin (CaM), and troponin C (TnC). The NMR structure of CaBP4 reveals an unusual closed conformation for the Ca2+-bound N-domain in contrast to an open conformation for the C-domain, suggesting that the two domains might have different functional roles in regulating target proteins. The Ca2+-bound C-domain (in both CaBP1 and CaBP4) exposes extensive hydrophobic patches during the Ca2+-induced closed to open conformational transition, which is similar to Ca2+-induced opening in CaM or other calcim sensor proteins. I performed a series of biophysical studies to characterize the binding of CaBP4 to the IQ motif of Cav1.4. These studies demonstrate that the Ca2+-bound C-domain (with an open conformation) interacts with a helical IQ motif similar to that seen previously for CaM. For the N-domain which adopts a Ca2+-bound closed conformation, I propose that the closed N-domain (for both CaBP1 and CaBP4) might undergo an induced-fit opening only in the presence of a particular target protein. Thus, this unique Ca2+-bound closed conformation of CaBP1 and CaBP4 may prevent the accidental binding to CaM target motifs and explain why both CaBP1 and CaBP4 have much higher target specificity than CaM.

Download or read book Neurotransmitter Release written by Hugo J. Bellen and published by Oxford University Press, USA. This book was released on 1999 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the reader with background information on neurotransmitter release. Emphasis is placed on the rationale by which proteins are assigned specific functions rather than just providing facts about function.

Download or read book Neuronal Calcium Sensor Proteins written by Pavel P. Philippov and published by Nova Publishers. This book was released on 2006 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Calcium signalling is an astonishing example how a simple caption can trigger and regulate an enormous variety of cellular and physiological responses. Ca2+-signalling routes very often involve Ca2+-binding proteins that sense changes in intracellular [Ca2+] and trigger cellular responses by regulating specific targets. One fascinating group among these Ca2+-sensors are the neuronal calcium sensor (NCS) proteins, named for their localisation in neuronal tissue (although there are reports of their expression in non-neuronal tissues as well). While recent excellent reviews have covered key aspects of this protein group, the field expanded in recent years making it more and more difficult to represent every facet of this ongoing research endeavour. This book is intended to represent properties of NCS proteins.

Download or read book Signal Transduction in the Retina written by Steven J. Fliesler and published by CRC Press. This book was released on 2007-12-26 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the twenty-first century, we are just beginning to understand more clearly the enormous diversity and complexity of signaling processes in the retina. Integrating advances in the biochemistry, cell biology, physiology, and physics of phototransduction, Signal Transduction in the Retina presents the methodologies and experimental approache

Download or read book Low voltage activated T type Calcium Channels written by Richard W. Tsien and published by . This book was released on 1998 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: