The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing

Peripheral myelin protein 22 (PMP22)
is a tetraspan membrane protein
strongly expressed in myelinating Schwann cells of the peripheral
nervous system. Myriad missense mutations in PMP22 result in varying
degrees of peripheral neuropathy. We used Rosetta 3.5 to generate
a homology model of PMP22 based on the recently published crystal
structure of claudin-15. The model suggests that several mutations
known to result in neuropathy act by disrupting transmembrane helix
packing interactions. Our model also supports suggestions from previous
studies that the first transmembrane helix is not tightly associated
with the rest of the helical bundle.