The homology model of PMP22 suggests mutations resulting in peripheral neuropathy disrupt transmembrane helix packing.

Mittendorf KF, Kroncke BM, Meiler J, Sanders CR
Biochemistry. 2014 53 (39): 6139-41

PMID: 25243937 · PMCID: PMC4188248 · DOI:10.1021/bi500809t

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.

MeSH Terms (12)

Amino Acid Sequence Claudins Crystallography, X-Ray Models, Molecular Molecular Sequence Data Mutation Myelin Proteins Peripheral Nervous System Diseases Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Sequence Homology, Amino Acid

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