| 2005 |
CaBP1 binds Mg2+ constitutively at EF-1 (Kd ~300 µM) and binds Ca2+ cooperatively at EF-3 and EF-4 (Kd ~2.5 µM); no Ca2+ binding detected at EF-2. Mg2+ and Ca2+ induce distinct conformational changes that promote protein dimerization and increased folding stability, suggesting CaBP1 switches between structurally distinct Mg2+-bound and Ca2+-bound states in response to Ca2+ signaling. |
NMR spectroscopy, isothermal titration calorimetry (ITC), and other biophysical analyses of recombinant CaBP1 |
The Journal of biological chemistry |
High |
16147998
|
| 2008 |
NMR structures of CaBP1 in Mg2+-bound and Ca2+-bound states show the N-domain (EF1/EF2) adopts a closed conformation with Mg2+ at EF1, while the C-domain undergoes a Ca2+-induced closed-to-open transition (like calmodulin), exposing hydrophobic residues (Leu132, His134, Ile141, Ile144, Val148). Ca2+-bound CaBP1 C-domain binds the N-terminal suppressor and ligand-binding core domains of InsP3R1 (residues 1–587) via ITC, whereas the CaBP1 N-domain and calmodulin did not show appreciable binding under these conditions. |
NMR structure determination, isothermal titration calorimetry |
The Journal of biological chemistry |
High |
19008222
|
| 2013 |
CaBP1 inhibits InsP3R activity by clamping intersubunit interactions: the CaBP1 C-lobe binds the β-domain of the InsP3-binding core of InsP3R1 via a hydrophobic cluster (V101, L104, V162 on CaBP1; L302, I364, L393 on InsP3R). CaBP1 promotes the intersubunit interface between the suppressor domain and the InsP3-binding core β-domain, the same interface that InsP3 disrupts to initiate gating. Thus CaBP1 slows InsP3R opening by restricting the conformational changes required for gating, and this inhibition is enhanced by Ca2+ binding to both CaBP1 and InsP3R. |
NMR paramagnetic relaxation enhancement, targeted cross-linking, Ca2+ flux assays, mutagenesis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23650371
|
| 2010 |
CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and induces calcium-dependent facilitation (CDF) through two structurally separable modules: the CaBP1 C-lobe anchors to the CaV1.2 IQ domain (overlapping with Ca2+/CaM C-lobe binding site), while the N-lobe together with interlobe linker residue Glu94 mediates CDI inhibition and CDF. Unlike CaM, functional CaBP1 EF-hands are not required for CDI inhibition. |
Crystal/structural analysis, electrophysiology, mutagenesis, binding assays |
Structure (London, England : 1993) |
High |
21134641
|
| 2013 |
CaM and CaBP1 compete directly for the CaV1 IQ domain via their apo (Ca2+-free) states, and the ratio of their apo-state binding affinities quantitatively predicts the functional outcome (CDI vs. CDI inhibition). Ca2+/CaM achieves sub-picomolar affinity for the IQ domain. Covalent tethering of CaM to the channel completely blocks this competition. |
Isothermal titration calorimetry, cell-based electrophysiology, mathematical modeling, covalent CaM tethering |
Journal of molecular biology |
High |
23811053
|
| 2011 |
CaBP1 interacts with the distal third of the CaV1.2 α1C N-terminal domain in a Ca2+-independent manner (distinct from the calmodulin-binding site in the N-terminus). CaBP1 also enhances voltage-dependent inactivation (VDI) and causes a depolarizing shift in voltage-dependent activation of CaV1.2. A proximal N-terminal segment separate from the CaBP1-binding site is required for transduction of the VDI effect, indicating modular organization of the N-terminal domain. |
Pull-down binding assays, electrophysiology of alternatively spliced CaV1.2 isoforms, deletion analysis |
The Journal of biological chemistry |
Medium |
21383011
|
| 2007 |
CaBP1 binds to the IQ motifs in the myo1c regulatory domain, competing with calmodulin for these sites; CaBP1 has higher apparent affinity for myo1c than CIB1, and both proteins compete better with calmodulin in the presence of calcium. CaBP1 and myo1c colocalize in cells as shown by fluorescence microscopy, and their interaction was confirmed by pull-down experiments with endogenous proteins. |
Pull-down assays, fluorescence microscopy colocalization, competition binding assays |
Journal of muscle research and cell motility |
Medium |
17994197
|
| 2006 |
L-CaBP1 (the long isoform of neuronal CaBP1) pulls down ARF1, Ca2+-dependent activator protein for secretion 1 (CAPS1), cyclic nucleotide 3′,5′-phosphodiesterase, vacuolar ATPase, AP1 and AP2 complexes, and the type I TGF-β receptor from bovine brain extracts in a Ca2+-dependent manner; some interactions were specific to CaBP1 and did not overlap with known calmodulin-binding proteins. |
GST pull-down from bovine brain cytosol/membrane extracts, MALDI-MS, Western blotting |
Proteomics |
Low |
16470652
|
| 2018 |
In cochlear spiral ganglion neurons (SGNs) from CaBP1 knockout mice, CaV1 (L-type) Ca2+ currents exhibit greater Ca2+-dependent inactivation (CDI) than wild-type, confirming that endogenous CaBP1 suppresses CDI of CaV1 channels in native neurons. Loss of CaBP1 also blunts activity-dependent repression of neurite growth and reduces CaV1-mediated phosphorylation of CREB, establishing that CaBP1 couples CaV1 channel activity to downstream transcriptional signaling. |
Whole-cell patch clamp electrophysiology in CaBP1 KO SGNs, neurite growth assays, CREB phosphorylation measurements |
Molecular and cellular neurosciences |
Medium |
29548764
|
| 2018 |
In CaBP1 KO mice, auditory brainstem response (ABR) wave I is larger in amplitude and shorter in latency, consistent with enhanced synchrony of auditory nerve fibers, and spiral ganglion neurons show greater excitability in patch-clamp recordings. Normal presynaptic function of inner hair cells is retained in CaBP1 KO mice, suggesting CaBP1 acts postsynaptically in spiral ganglion neurons rather than at the IHC presynapse. |
ABR recordings, whole-cell patch clamp of spiral ganglion neurons, auditory physiology in KO mice |
Hearing research |
Medium |
29661613
|
| 2024 |
CaBP1 and CaBP2 act cooperatively to suppress both voltage-dependent and calcium-dependent inactivation of CaV1.3 channels in inner hair cells (IHCs). In Cabp1/2 double-knockout mice, CaV1.3 inactivation is strongly enhanced, recovery from inactivation is slowed, and sustained exocytosis is severely impaired; transgenic re-expression of CaBP2 alone substantially rescues IHC synaptic function and hearing, demonstrating partial functional redundancy. |
Patch-clamp electrophysiology (CaV1.3 current recordings), exocytosis measurements, in vivo auditory recordings in double-KO and rescue transgenic mice |
eLife |
High |
39718549
|
| 2016 |
CaBP1/caldendrin knockout mice show altered retinal ganglion cell light responses (differences in amplitude and kinetics) despite normal gross retinal morphology, normal synapse ribbon counts, and normal ribbon synapse ultrastructure, indicating CaBP1/caldendrin is required for proper transmission of light responses through the retina, likely via presynaptic Ca2+-dependent signaling modulation. |
Whole-cell patch clamp of retinal ganglion cells in Cabp1 KO mice, immunohistochemistry, transmission electron microscopy |
eNeuro |
Medium |
27822497
|
| 2026 |
NMR structures of Ca2+-CaBP1 bound to the CaV1.2 IQ-motif peptide identify specific contact residues: CaBP1 residues A107, F111, M128, L131, I144, and M165 contact IQ residues I1654, Y1657, and F1658, with a salt bridge between IQ K1662 and CaBP1 D140. Ca2+ binding to CaBP1 is enhanced >40-fold when CaBP1 is bound to the IQ peptide; the IQ peptide binds Ca2+-bound CaBP1 with ~100-fold higher affinity (Kd ~45 nM) than Ca2+-free CaBP1. Electrophysiology suggests CaBP1 increases CaV1.2 channel open probability. |
NMR structure determination, ITC binding assays, mutagenesis (K1662 charge reversal), electrophysiology |
Biochemistry |
High |
41859936
|