AI Article Synopsis
- * The study presents NMR structures showing how CaBP4 changes shape when bound to either Mg²⁺ or Ca²⁺, with two distinct lobes and a flexible N-terminal region.
- * Specific amino acids on CaBP4 interact with the IQ motif of the calcium channel Cav1.4, and a mutation in Cav1.4 (Y1595E) disrupts this interaction, suggesting that CaBP4 may help activate the channel by altering its inhibitory connections. *
Article Abstract
CaBP4 modulates Ca(2+)-dependent activity of L-type voltage-gated Ca(2+) channels (Cav1.4) in retinal photoreceptor cells. Mg(2+) binds to the first and third EF-hands (EF1 and EF3), and Ca(2+) binds to EF1, EF3, and EF4 of CaBP4. Here we present NMR structures of CaBP4 in both Mg(2+)-bound and Ca(2+)-bound states and model the CaBP4 structural interaction with Cav1.4. CaBP4 contains an unstructured N-terminal region (residues 1-99) and four EF-hands in two separate lobes. The N-lobe consists of EF1 and EF2 in a closed conformation with either Mg(2+) or Ca(2+) bound at EF1. The C-lobe binds Ca(2+) at EF3 and EF4 and exhibits a Ca(2+)-induced closed-to-open transition like that of calmodulin. Exposed residues in Ca(2+)-bound CaBP4 (Phe(137), Glu(168), Leu(207), Phe(214), Met(251), Phe(264), and Leu(268)) make contacts with the IQ motif in Cav1.4, and the Cav1.4 mutant Y1595E strongly impairs binding to CaBP4. We conclude that CaBP4 forms a collapsed structure around the IQ motif in Cav1.4 that we suggest may promote channel activation by disrupting an interaction between IQ and the inhibitor of Ca(2+)-dependent inactivation domain.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223327 | PMC |
| http://dx.doi.org/10.1074/jbc.M114.604439 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SPHK2 Knockdown Inhibits the Proliferation and Migration of Fibroblast-Like Synoviocytes Through the IL-17 Signaling Pathway in Osteoarthritis.
J Inflamm Res
October 2024
Department of Sports Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou City, Hainan Province, 570311, People's Republic of China.
Objective: Synovial inflammation is vital for the progression of osteoarthritis (OA). The objective of this study was to explore the effects and potential molecular mechanisms of sphingosine kinase 2 (SPHK2) on the proliferation and migration of fibroblast-like synoviocytes (FLS).
Methods: A TNF-α-stimulated FLS model and a papain-induced OA rat model were constructed.
Comprehensive Characterization of a Subfamily of Ca-Binding Proteins in Mouse and Human Retinal Neurons at Single-Cell Resolution.
eNeuro
September 2024
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou 325000, China
Ca-binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons.
View Article and Find Full Text PDFA novel homozygous nonsense variant in causing stationary cone/rod synaptic dysfunction.
Ophthalmic Genet
December 2024
Harvard Medical School Department of Ophthalmology, Retina Service, Massachusetts Eye and Ear, Boston, Massachusetts, USA.
Introduction: Variants in the gene cause a phenotype to be included in the spectrum of congenital stationary night blindness, though some reports suggest that the clinical abnormalities are more accurately categorized as a synaptic disease of the cones and rods. We report a novel homozygous nonsense variant in in a patient complaining of non-progressive reduced visual acuity and photophobia but not nyctalopia.
Methods: Complete ocular examination, fundus photographs, autofluorescence, optical coherence tomography, electroretinography, and targeted sequencing of known inherited retinal disease-associated genes.
Pathogenic genes implicated in sleep-related hypermotor epilepsy: a research progress update.
Front Neurol
June 2024
Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by a variable age of onset and heterogeneous etiology. Current literature suggests a prevalence rate of approximately 1.8 per 100,000 persons.
View Article and Find Full Text PDFmutation in mice shows alteration in protein expression level and neuron discharge frequency.
Transl Pediatr
May 2024
School of Medicine, South China University of Technology, Guangzhou, China.
Background: The calcium-binding protein 4 () gene is a newly identified epilepsy-related gene that might be associated with a rare type of genetic focal epilepsy; that is, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). , mutant CABP4 causes an increased inward flow voltage of calcium ions and a significant increase in the electrical signal discharge in hippocampus neurons; however, the role of in epilepsy has not yet been specifically described, and there is not yet a CABP4 mutant animal model recapitulating the epilepsy phenotype.
Methods: We introduced a human missense mutation into the C57BL/6J mouse genome and generated a knock-in strain carrying a glycine-to-aspartic acid mutation in the gene.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!