8iia
From Proteopedia
Crystal structure of the oligomeric state of the extracellular domain of human myelin protein zero(MPZ/P0)
Structural highlights
DiseaseMYP0_HUMAN Palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome;Autosomal dominant intermediate Charcot-Marie-Tooth disease type D;Autosomal dominant Charcot-Marie-Tooth disease type 2I;Roussy-Levy syndrome;Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain;Dejerine-Sottas syndrome;Charcot-Marie-Tooth disease type 1B;Autosomal dominant Charcot-Marie-Tooth disease type 2J. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionMYP0_HUMAN Is an adhesion molecule necessary for normal myelination in the peripheral nervous system. It mediates adhesion between adjacent myelin wraps and ultimately drives myelin compaction.[1] [2] Publication Abstract from PubMedMyelin protein zero (MPZ or P0) is a transmembrane protein which functions to glue membranes in peripheral myelin. Inter-membrane adhesion is mediated by homophilic interactions between the extracellular domains (ECDs) of MPZ. Single amino acid substitutions in an ECD cause demyelinating neuropathy, Charcot-Marie-Tooth disease (CMT), with unknown mechanisms. In this study, by using a novel assay system "nanomyelin," we revealed that a stacked-rings-like ECD-8-mer is responsible for membrane adhesion. Two inter-ECD interactions, cis and head-to-head, are essential to constituting the 8-mer and to gluing the membranes. This result was reinforced by the observation that the CMT-related N87H substitution at the cis interface abolished membrane-adhesion activity. In contrast, the CMT-related D32G and E68V variants retained membrane-stacking activity, whereas their thermal stability was lower than that of the WT. Reduced thermal stability may lead to impairment of the long-term stability of ECD and the layered membranes of myelin. Structural bases for the Charcot-Marie-Tooth disease induced by single amino acid substitutions of myelin protein zero.,Sakakura M, Tanabe M, Mori M, Takahashi H, Mio K Structure. 2023 Nov 2;31(11):1452-1462.e4. doi: 10.1016/j.str.2023.08.016. Epub , 2023 Sep 11. PMID:37699394[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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