A "Tug of War" Maintains a Dynamic Protein-Membrane Complex : Molecular Dynamics Simulations of C-Raf RBD-CRD Bound to K-Ras4B at an Anionic Membrane
Association of Raf kinase with activated Ras triggers downstream signaling cascades toward regulating transcription in the cells' nucleus. Dysregulation of Ras-Raf signaling stimulates cancers. We investigate the C-Raf RBD and CRD regions when bound to oncogenic K-Ras4B at the membrane. All-atom molecular dynamics simulations suggest that the membrane plays an integral role in regulating the configurational ensemble of the complex. Remarkably, the complex samples a few states dynamically, reflecting a competition between C-Raf CRD- and K-Ras4B- membrane interactions. This competition arises because the interaction between the RBD and K-Ras is strong while the linker between the RBD and CRD is short. Such a mechanism maintains a modest binding for the overall complex at the membrane and is expected to facilitate fast signaling processes. Competition of protein-membrane contacts is likely a common mechanism for other multiprotein complexes, if not multidomain proteins at membranes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
ACS central science - 4(2018), 2 vom: 28. Feb., Seite 298-305 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Zhen-Lu [VerfasserIn] |
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| Anmerkungen: |
Date Revised 01.10.2020 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1021/acscentsci.7b00593 |
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NLM281884595 |
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| 100 | 1 | |a Li, Zhen-Lu |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A "Tug of War" Maintains a Dynamic Protein-Membrane Complex |b Molecular Dynamics Simulations of C-Raf RBD-CRD Bound to K-Ras4B at an Anionic Membrane |
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| 520 | |a Association of Raf kinase with activated Ras triggers downstream signaling cascades toward regulating transcription in the cells' nucleus. Dysregulation of Ras-Raf signaling stimulates cancers. We investigate the C-Raf RBD and CRD regions when bound to oncogenic K-Ras4B at the membrane. All-atom molecular dynamics simulations suggest that the membrane plays an integral role in regulating the configurational ensemble of the complex. Remarkably, the complex samples a few states dynamically, reflecting a competition between C-Raf CRD- and K-Ras4B- membrane interactions. This competition arises because the interaction between the RBD and K-Ras is strong while the linker between the RBD and CRD is short. Such a mechanism maintains a modest binding for the overall complex at the membrane and is expected to facilitate fast signaling processes. Competition of protein-membrane contacts is likely a common mechanism for other multiprotein complexes, if not multidomain proteins at membranes | ||
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| 700 | 1 | |a Buck, Matthias |e verfasserin |4 aut | |
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