title: The homology model of PMP22 suggests mutations resulting in peripheral neuropathy disrupt transmembrane helix packing.
abstract: 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.
authors.affiliation: Department of Biochemistry, ‡Center for Structural Biology, and §Departments of Pharmacology and Bioinformatics, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Mittendorf
authors.forename: Brett M
authors.initials: BM
authors.lastname: Kroncke
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
authors.forename: Charles R
authors.initials: CR
authors.lastname: Sanders
mesh_terms: D000595:Amino Acid Sequence; D057167:Claudins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D057167:Claudins; D009185:Myelin Proteins; C073687:PMP22 protein, human; C459596:claudin 15