ArticleScientific reports2017
Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in human myelin protein P2.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Identification of suicide brain transcriptomic signatures using meta-analysis of multiple cohorts.Translational psychiatry · 2026Pooled it
- Human Peripheral Myelin Protein 2 and Charcot-Marie-Tooth Disease or Structural Missense Variants Show Different Binding to Myelin-Like Lipid Monolayers.Chembiochem : a European journal of chemical biology · 2026Article
- Mechanobiology of Myelin Generation/Regeneration in Health and Disease.Results and problems in cell differentiation · 2026Review
- On the synergy between myelin proteins P0, MBP, and P2 in peripheral nerve major dense line formation.The FEBS journal · 2025Article
- Article
- Acrylamide, Applied During Pregnancy and Postpartum Period in Offspring Rats, Significantly Disrupted Myelination by Decreasing the Levels of Myelin-Related Proteins: MBP, MAG, and MOG.Neurochemical research · 2024Article
- Molecular Mimicry between Meningococcal B Factor H-Binding Protein and Human Proteins.Global medical genetics · 2023Article
- A Novel Family with Demyelinating Charcot-Marie-Tooth Disease Caused by a Mutation in the PMP2 Gene: A Case Series of Nine Patients and a Brief Review of the Literature.Children (Basel, Switzerland) · 2023Article
- Multi-Omic Profiling, Structural Characterization, and Potent Inhibitor Screening of Evasion-Related Proteins of a Parasitic Nematode,Biomedicines · 2023Article
- Conserved intramolecular networks in GDAP1 are closely connected to CMT-linked mutations and protein stability.PloS one · 2023Article
- Structural insights into Charcot-Marie-Tooth disease-linked mutations in human GDAP1.FEBS open bio · 2022Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- How Does Protein Zero Assemble Compact Myelin?Cells · 2020Article
- Article
- A myelin sheath protein forming its lattice.The Journal of biological chemistry · 2020Article
- Cryo-EM, X-ray diffraction, and atomistic simulations reveal determinants for the formation of a supramolecular myelin-like proteolipid lattice.The Journal of biological chemistry · 2020Article
- Sub-Atomic Resolution Crystal Structures Reveal Conserved Geometric Outliers at Functional Sites.Molecules (Basel, Switzerland) · 2019Article
- Peripheral myelin protein 2 - a novel cluster of mutations causing Charcot-Marie-Tooth neuropathy.Orphanet journal of rare diseases · 2019Article
- Molecular structure and function of myelin protein P0 in membrane stacking.Scientific reports · 2019Article
- Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F.Frontiers in molecular neuroscience · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuropathies. Recently, three CMT1-associated point mutations (I43N, T51P, and I52T) were discovered in the abundant peripheral myelin protein P2. These mutations trigger abnormal myelin structure, leading to reduced nerve conduction velocity, muscle weakness, and distal limb atrophy. P2 is a myelin-specific protein expressed by Schwann cells that binds to fatty acids and membranes, contributing to peripheral myelin lipid homeostasis. We studied the molecular basis of the P2 patient mutations. None of the CMT1-associated mutations alter the overall folding of P2 in the crystal state. P2 disease variants show increased aggregation tendency and remarkably reduced stability, T51P being most severe. In addition, P2 disease mutations affect protein dynamics. Both fatty acid binding by P2 and the kinetics of its membrane interactions are affected by the mutations. Experiments and simulations suggest opening of the β barrel in T51P, possibly representing a general mechanism in fatty acid-binding proteins. Our findings demonstrate that altered biophysical properties and functional dynamics of P2 may cause myelin defects in CMT1 patients. At the molecular level, a few malformed hydrogen bonds lead to structural instability and misregulation of conformational changes related to ligand exchange and membrane binding.
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