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

[Image: see text] 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 m...

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Autores principales: Mittendorf, Kathleen F., Kroncke, Brett M., Meiler, Jens, Sanders, Charles R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188248/
https://www.ncbi.nlm.nih.gov/pubmed/25243937
http://dx.doi.org/10.1021/bi500809t
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author Mittendorf, Kathleen F.
Kroncke, Brett M.
Meiler, Jens
Sanders, Charles R.
author_facet Mittendorf, Kathleen F.
Kroncke, Brett M.
Meiler, Jens
Sanders, Charles R.
author_sort Mittendorf, Kathleen F.
collection PubMed
description [Image: see text] 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.
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spelling pubmed-41882482015-09-22 The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing Mittendorf, Kathleen F. Kroncke, Brett M. Meiler, Jens Sanders, Charles R. Biochemistry [Image: see text] 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. American Chemical Society 2014-09-22 2014-10-07 /pmc/articles/PMC4188248/ /pubmed/25243937 http://dx.doi.org/10.1021/bi500809t Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Mittendorf, Kathleen F.
Kroncke, Brett M.
Meiler, Jens
Sanders, Charles R.
The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing
title The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing
title_full The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing
title_fullStr The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing
title_full_unstemmed The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing
title_short The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing
title_sort homology model of pmp22 suggests mutations resulting in peripheral neuropathy disrupt transmembrane helix packing
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188248/
https://www.ncbi.nlm.nih.gov/pubmed/25243937
http://dx.doi.org/10.1021/bi500809t
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