Myelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding and molecular conformation.
TLDR
A detailed picture of the CNPase active site during its catalytic cycle is provided, and a specific function for the previously uncharacterized N-terminal domain is suggested.Abstract:
The 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) is a highly abundant membrane-associated enzyme in the myelin sheath of the vertebrate nervous system. CNPase is a member of the 2H phosphoesterase family and catalyzes the formation of 2′-nucleotide products from 2′,3′-cyclic substrates; however, its physiological substrate and function remain unknown. It is likely that CNPase participates in RNA metabolism in the myelinating cell. We solved crystal structures of the phosphodiesterase domain of mouse CNPase, showing the binding mode of nucleotide ligands in the active site. The binding mode of the product 2′-AMP provides a detailed view of the reaction mechanism. Comparisons of CNPase crystal structures highlight flexible loops, which could play roles in substrate recognition; large differences in the active-site vicinity are observed when comparing more distant members of the 2H family. We also studied the full-length CNPase, showing its N-terminal domain is involved in RNA binding and dimerization. Our results provide a detailed picture of the CNPase active site during its catalytic cycle, and suggest a specific function for the previously uncharacterized N-terminal domain.read more
Citations
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Myelination of the nervous system: mechanisms and functions
Klaus-Armin Nave,Hauke B. Werner +1 more
TL;DR: Recent advances in the understanding of myelin biogenesis, its lifelong plasticity, and the reciprocal interactions of myelinating glia with the axons they ensheath are highlighted.
Journal ArticleDOI
Myelin-specific proteins: a structurally diverse group of membrane-interacting molecules.
TL;DR: A detailed understanding of myelin protein structure and function at the molecular level will be required to fully grasp their physiological roles in the myelin sheath.
Journal ArticleDOI
Oligodendrocyte morphometry and expression of myelin – Related mRNA in ventral prefrontal white matter in major depressive disorder
Grazyna Rajkowska,Gouri Mahajan,Dorota Maciag,Monica Sathyanesan,Abiye H. Iyo,Mohadetheh Moulana,Patrick B. Kyle,William L. Woolverton,Jose Javier Miguel-Hidalgo,Craig A. Stockmeier,Samuel S. Newton +10 more
TL;DR: Altered expression of four myelin genes and CNPase protein suggests a mechanism for the degeneration of cortical axons and dysfunctional maturation of oligodendrocytes in MDD.
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Electron microscopy of myelin: Structure preservation by high-pressure freezing
TL;DR: Cryofixation has proven well suited to yield both, improved contrast and excellent preservation of structural detail of the axon/myelin-unit in healthy and mutant mice and can also be applied to other model organisms, including aquatic species.
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