8IIA

Crystal structure of the oligomeric state of the extracellular domain of human myelin protein zero(MPZ/P0)

Summary for 8IIA

• Entry DOI: 10.2210/pdb8iia/pdb
• Descriptor: Myelin protein P0, GLYCEROL (3 entities in total)
• Functional Keywords: membrane adhesion, oligomeric state, cell adhesion
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 14158.74

Authors

Sakakura, M.,Tanabe, M.,Mio, K. (deposition date: 2023-02-24, release date: 2023-08-30, Last modification date: 2024-10-30)

Primary citation

Sakakura, M.,Tanabe, M.,Mori, M.,Takahashi, H.,Mio, K.
Structural bases for the Charcot-Marie-Tooth disease induced by single amino acid substitutions of myelin protein zero.
Structure, 31:1452-, 2023

PubMed Abstract: Myelin 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.

PubMed: 37699394
DOI: 10.1016/j.str.2023.08.016

Experimental method

X-RAY DIFFRACTION (2.09 Å)