Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization.
Oligomerization of transmembrane (TM) helices is a key stage in the folding of membrane proteins. Glycophorin A (GpA) is a well-documented test system for this process. Coarse-grained molecular dynamics (CG-MD) allows us to simulate the self-assembly of TM helices into dimers, for both wild-type (WT...
| Main Authors: | , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2008
|
| _version_ | 1797075704902320128 |
|---|---|
| author | Psachoulia, E Fowler, P Bond, P Sansom, MS |
| author_facet | Psachoulia, E Fowler, P Bond, P Sansom, MS |
| author_sort | Psachoulia, E |
| collection | OXFORD |
| description | Oligomerization of transmembrane (TM) helices is a key stage in the folding of membrane proteins. Glycophorin A (GpA) is a well-documented test system for this process. Coarse-grained molecular dynamics (CG-MD) allows us to simulate the self-assembly of TM helices into dimers, for both wild-type (WT) and mutant GpA sequences. For the WT sequences, dimers formed rapidly and remained stable in all simulations. The resultant dimers exhibited right-handed crossing and the same interhelix contacts as in NMR structures. Simulations of disruptive mutants revealed the dimers were less stable, with values of DeltaDelta G dimerization consistent with experimental data. The dimers of disruptive mutants were distorted relative to the WT and showed left-handed crossing of their helices. CG-MD can therefore be used to explore the interactions of TM helices, an important stage in the folding of membrane proteins. In particular, CG-MD has been shown to be sensitive enough to detect disruptions introduced by mutation. Future refinement of such models via atomistic simulations will enable a multiscale approach to predict the folding of membrane proteins. |
| first_indexed | 2024-03-06T23:54:02Z |
| format | Journal article |
| id | oxford-uuid:7398300b-c1a3-481d-8b1f-90b3b601bd87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:54:02Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:7398300b-c1a3-481d-8b1f-90b3b601bd872022-03-26T19:57:25ZHelix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7398300b-c1a3-481d-8b1f-90b3b601bd87EnglishSymplectic Elements at Oxford2008Psachoulia, EFowler, PBond, PSansom, MSOligomerization of transmembrane (TM) helices is a key stage in the folding of membrane proteins. Glycophorin A (GpA) is a well-documented test system for this process. Coarse-grained molecular dynamics (CG-MD) allows us to simulate the self-assembly of TM helices into dimers, for both wild-type (WT) and mutant GpA sequences. For the WT sequences, dimers formed rapidly and remained stable in all simulations. The resultant dimers exhibited right-handed crossing and the same interhelix contacts as in NMR structures. Simulations of disruptive mutants revealed the dimers were less stable, with values of DeltaDelta G dimerization consistent with experimental data. The dimers of disruptive mutants were distorted relative to the WT and showed left-handed crossing of their helices. CG-MD can therefore be used to explore the interactions of TM helices, an important stage in the folding of membrane proteins. In particular, CG-MD has been shown to be sensitive enough to detect disruptions introduced by mutation. Future refinement of such models via atomistic simulations will enable a multiscale approach to predict the folding of membrane proteins. |
| spellingShingle | Psachoulia, E Fowler, P Bond, P Sansom, MS Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. |
| title | Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. |
| title_full | Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. |
| title_fullStr | Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. |
| title_full_unstemmed | Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. |
| title_short | Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. |
| title_sort | helix helix interactions in membrane proteins coarse grained simulations of glycophorin a helix dimerization |
| work_keys_str_mv | AT psachouliae helixhelixinteractionsinmembraneproteinscoarsegrainedsimulationsofglycophorinahelixdimerization AT fowlerp helixhelixinteractionsinmembraneproteinscoarsegrainedsimulationsofglycophorinahelixdimerization AT bondp helixhelixinteractionsinmembraneproteinscoarsegrainedsimulationsofglycophorinahelixdimerization AT sansomms helixhelixinteractionsinmembraneproteinscoarsegrainedsimulationsofglycophorinahelixdimerization |