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Mutations in demyelinating peripheral neuropathies support molecular model of myelin PO‐glycoprotein extracellular domain
Author(s) -
Kirschner D. A.,
Saavedra R. A.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490390109
Subject(s) - myelin , glycoprotein , extracellular , myelin associated glycoprotein , amino acid , chemistry , microbiology and biotechnology , point mutation , biophysics , biochemistry , biology , gene , mutant , neuroscience , central nervous system
Homophilic interactions of the major integral membrane protein of peripheral nerve myelin, P0‐glycoprotein, are thought to mediate membrane adhesion and compaction. Molecular modeling of its extracellular domain (P0‐ED), based on its resemblance to an immunoglobulin variable domain and on X‐ray diffraction measuements of inter‐membrane spacings of myelin, has suggested which amino acid sidechains may be involved in the homophilic adhesion. Recently identified point‐mutations in the human P0 gene result in amino acid substitutions in P0 protein and correlate with demyelinating motor and sensory neuropathies. The molecular model explains how these changes result in disrupted P0‐P0 interactions; indicates how compensatory changes in amino acids, as occur in P0‐ED of other species, preserve normal homophilic interactions; and predicts what other residue substitutions might underlie additional cases of demyelinating neuropathies. Copyright © 1994 Wiley‐Liss, Inc.