ArticleBiochemistry2008
The peripheral neuropathy-linked Trembler and Trembler-J mutant forms of peripheral myelin protein 22 are folding-destabilized.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Functional ultrasound and brain connectivity reveal central nervous system compromise in Trembler-J mice model of Charcot-Marie-Tooth disease.Scientific reports · 2024Article
- Folding speeds of helical membrane proteins.Biochemical Society transactions · 2024Review
- Implantable Electroceutical Approach Improves Myelination by Restoring Membrane Integrity in a Mouse Model of Peripheral Demyelinating Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Expanding the phenotypic spectrum of Dejerine-Sottas syndrome caused by the trembler mutation.Neurogenetics · 2022Article
- Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture.Biomolecules · 2022Article
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- Membrane proteins enter the fold.Current opinion in structural biology · 2021Review
- Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests.Biomolecules · 2021Article
- Peripheral myelin protein 22 modulates store-operated calcium channel activity, providing insights into Charcot-Marie-Tooth disease etiology.The Journal of biological chemistry · 2019Article
- Aminosalicylic acid reduces ER stress and Schwann cell death induced by MPZ mutations.International journal of molecular medicine · 2019Article
- Peripheral myelin protein 22 alters membrane architecture.Science advances · 2017Article
- Conformational Stability and Pathogenic Misfolding of the Integral Membrane Protein PMP22.Journal of the American Chemical Society · 2015Article
- Influence of Pathogenic Mutations on the Energetics of Translocon-Mediated Bilayer Integration of Transmembrane Helices.The Journal of membrane biology · 2015Article
- The safety dance: biophysics of membrane protein folding and misfolding in a cellular context.Quarterly reviews of biophysics · 2015Article
- The homology model of PMP22 suggests mutations resulting in peripheral neuropathy disrupt transmembrane helix packing.Biochemistry · 2014Article
- Reversible folding of human peripheral myelin protein 22, a tetraspan membrane protein.Biochemistry · 2013Article
- The PMP22 gene and its related diseases.Molecular neurobiology · 2013Review
- Protein misfolding and clearance in demyelinating peripheral neuropathies: Therapeutic implications.Communicative & integrative biology · 2012Article
- Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome-autophagy pathways.Journal of cell science · 2011Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Dominant mutations in the tetraspan membrane protein peripheral myelin protein 22 (PMP22) are known to result in peripheral neuropathies such as Charcot-Marie-Tooth type 1A (CMT1A) disease via mechanisms that appear to be closely linked to misfolding of PMP22 in the membrane of the endoplasmic reticulum (ER). To characterize the molecular defects in PMP22, we examined the structure and stability of two human disease mutant forms of PMP22 that are also the basis for mouse models of peripheral neuropathies: G150D ( Trembler phenotype) and L16P ( Trembler-J phenotype). Circular dichroism and NMR spectroscopic studies indicated that, when folded, the three-dimensional structures of these disease-linked mutants are similar to that of the folded wild-type protein. However, the folded forms of the mutants were observed to be destabilized relative to the wild-type protein, with the L16P mutant being particularly unstable. The rate of refolding from an unfolded state was observed to be very slow for the wild-type protein, and no refolding was observed for either mutant. These results lead to the hypothesis that ER quality control recognizes the G150D and L16P mutant forms of PMP22 as defective through mechanisms closely related to their conformational instability and/or slow folding. It was also seen that wild-type PMP22 binds Zn(II) and Cu(II) with micromolar affinity, a property that may be important to the stability and function of this protein. Zn(II) was able to rescue the stability defect of the Tr mutant.
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