ArticleMolecular biology of the cell2012
Structure and functional studies of N-terminal Cx43 mutants linked to oculodentodigital dysplasia.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- Two novel GJA1 variants in oculodentodigital dysplasia.Molecular genetics & genomic medicine · 2019Trial
- Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures.Biology · 2024Review
- Article
- Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM.Nature communications · 2023Article
- Towards a Better Understanding of Genotype-Phenotype Correlations and Therapeutic Targets for Cardiocutaneous Genes: The Importance of Functional Studies above Prediction.International journal of molecular sciences · 2022Review
- Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids.Science advances · 2020Article
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Gap junction structure: unraveled, but not fully revealed.F1000Research · 2017Review
- Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry.Frontiers in physiology · 2017Article
- Specificity of the connexin W3/4 locus for functional gap junction formation.Channels (Austin, Tex.) · 2016Article
- Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia.Molecular biology of the cell · 2016Article
- Connexinopathies: a structural and functional glimpse.BMC cell biology · 2016Review
- Determinants of Cx43 Channel Gating and Permeation: The Amino Terminus.Biophysical journal · 2016Article
- Recent advances in understanding ichthyosis pathogenesis.F1000Research · 2016Review
- Erythrokeratodermia variabilis et progressiva allelic to oculo-dento-digital dysplasia.The Journal of investigative dermatology · 2015Article
- Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et Progressiva, without Features of Oculodentodigital Dysplasia.The Journal of investigative dermatology · 2015Article
- Helicobacter pylori VacA induces apoptosis by accumulation of connexin 43 in autophagic vesicles via a Rac1/ERK-dependent pathway.Cell death discovery · 2015Article
- Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system?Frontiers in pharmacology · 2013Review
- A novel autosomal recessive GJA1 missense mutation linked to Craniometaphyseal dysplasia.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the gene encoding connexin-43 (Cx43) cause the human development disorder known as oculodentodigital dysplasia (ODDD). In this study, ODDD-linked Cx43 N-terminal mutants formed nonfunctional gap junction-like plaques and exhibited dominant-negative effects on the coupling conductance of coexpressed endogenous Cx43 in reference cell models. Nuclear magnetic resonance (NMR) protein structure determination of an N-terminal 23-amino acid polypeptide of wild-type Cx43 revealed that it folded in to a kinked α-helical structure. This finding predicted that W4 might be critically important in intramolecular and intermolecular interactions. Thus we engineered and characterized a W4A mutant and found that this mutant formed a regular, nonkinked α-helix but did not form functional gap junctions. Furthermore, a G2V variant peptide of Cx43 showed a kinked helix that now included V2 interactions with W4, resulting in the G2V mutant forming nonfunctional gap junctions. Also predicted from the NMR structures, a G2S mutant was found to relieve these interactions and allowed the protein to form functional gap junctions. Collectively, these studies suggest that the nature of the mutation conveys loss of Cx43 function by distinctly different mechanisms that are rooted in the structure of the N-terminal region.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.