Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch
A novel mechanism for membrane modulation of transmembrane protein structure, and consequently function, is suggested in which mismatch between the hydrophobic surface of the protein and the hydrophobic interior of the lipid bilayer induces a flexing or bending of a transmembrane segment of the prot...
| Main Authors: | , , , |
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| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
Elsevier
2006
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| נושאים: |
| _version_ | 1826299761801560064 |
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| author | Philip L. Yeagle Michael Bennett Vincent Lemaître Watts, A. |
| author_facet | Philip L. Yeagle Michael Bennett Vincent Lemaître Watts, A. |
| author_sort | Philip L. Yeagle |
| collection | OXFORD |
| description | A novel mechanism for membrane modulation of transmembrane protein structure, and consequently function, is suggested in which mismatch between the hydrophobic surface of the protein and the hydrophobic interior of the lipid bilayer induces a flexing or bending of a transmembrane segment of the protein. Studies on model hydrophobic transmembrane peptides predict that helices tilt to submerge the hydrophobic surface within the lipid bilayer to satisfy the hydrophobic effect if the helix length exceeds the bilayer width. The hydrophobic surface of transmembrane helix 1 (TM1) of lactose permease, LacY, is accessible to the bilayer, and too long to be accommodated in the hydrophobic portion of a typical lipid bilayer if oriented perpendicular to the membrane surface. Hence, nuclear magnetic resonance (NMR) data and molecular dynamics simulations show that TM1 from LacY may flex as well as tilt to satisfy the hydrophobic mismatch with the bilayer. In an analogous study of the hydrophobic mismatch of TM7 of bovine rhodopsin, similar flexing of the transmembrane segment near the conserved NPxxY sequence is observed. As a control, NMR data on TM5 of lacY, which is much shorter than TM1, show that TM5 is likely to tilt, but not flex, consistent with the close match between the extent of hydrophobic surface of the peptide and the hydrophobic thickness of the bilayer. These data suggest mechanisms by which the lipid bilayer in which the protein is embedded modulates conformation, and thus function, of integral membrane proteins through interactions with the hydrophobic transmembrane helices. |
| first_indexed | 2024-03-07T05:06:51Z |
| format | Journal article |
| id | oxford-uuid:da396367-4f21-4604-9fa6-3e32389eb962 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:06:51Z |
| publishDate | 2006 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:da396367-4f21-4604-9fa6-3e32389eb9622022-03-27T09:01:39ZTransmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatchJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:da396367-4f21-4604-9fa6-3e32389eb962BiochemistryEnglishOxford University Research Archive - ValetElsevier2006Philip L. YeagleMichael BennettVincent LemaîtreWatts, A.A novel mechanism for membrane modulation of transmembrane protein structure, and consequently function, is suggested in which mismatch between the hydrophobic surface of the protein and the hydrophobic interior of the lipid bilayer induces a flexing or bending of a transmembrane segment of the protein. Studies on model hydrophobic transmembrane peptides predict that helices tilt to submerge the hydrophobic surface within the lipid bilayer to satisfy the hydrophobic effect if the helix length exceeds the bilayer width. The hydrophobic surface of transmembrane helix 1 (TM1) of lactose permease, LacY, is accessible to the bilayer, and too long to be accommodated in the hydrophobic portion of a typical lipid bilayer if oriented perpendicular to the membrane surface. Hence, nuclear magnetic resonance (NMR) data and molecular dynamics simulations show that TM1 from LacY may flex as well as tilt to satisfy the hydrophobic mismatch with the bilayer. In an analogous study of the hydrophobic mismatch of TM7 of bovine rhodopsin, similar flexing of the transmembrane segment near the conserved NPxxY sequence is observed. As a control, NMR data on TM5 of lacY, which is much shorter than TM1, show that TM5 is likely to tilt, but not flex, consistent with the close match between the extent of hydrophobic surface of the peptide and the hydrophobic thickness of the bilayer. These data suggest mechanisms by which the lipid bilayer in which the protein is embedded modulates conformation, and thus function, of integral membrane proteins through interactions with the hydrophobic transmembrane helices. |
| spellingShingle | Biochemistry Philip L. Yeagle Michael Bennett Vincent Lemaître Watts, A. Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| title | Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| title_full | Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| title_fullStr | Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| title_full_unstemmed | Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| title_short | Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| title_sort | transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch |
| topic | Biochemistry |
| work_keys_str_mv | AT philiplyeagle transmembranehelicesofmembraneproteinsmayflextosatisfyhydrophobicmismatch AT michaelbennett transmembranehelicesofmembraneproteinsmayflextosatisfyhydrophobicmismatch AT vincentlemaitre transmembranehelicesofmembraneproteinsmayflextosatisfyhydrophobicmismatch AT wattsa transmembranehelicesofmembraneproteinsmayflextosatisfyhydrophobicmismatch |