Integrative dynamic structural biology unveils conformers essential for the oligomerization of a large GTPase
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arXiv
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| Autori principali: | , , , , , , , , , , , , , |
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| Natura: | Preprint |
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2020
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| author | Peulen, Thomas-Otavio Hengstenberg, Carola S. Biehl, Ralf Dimura, Mykola Lorenz, Charlotte Valeri, Alessandro Ince, Semra Vöpel, Tobias Faragó, Bela Gohlke, Holger Klare, Johann P. Stadler, Andreas M. Seidel, Claus A. M. Herrmann, Christian |
| author_facet | Peulen, Thomas-Otavio Hengstenberg, Carola S. Biehl, Ralf Dimura, Mykola Lorenz, Charlotte Valeri, Alessandro Ince, Semra Vöpel, Tobias Faragó, Bela Gohlke, Holger Klare, Johann P. Stadler, Andreas M. Seidel, Claus A. M. Herrmann, Christian |
| contents | Guanylate binding proteins (GBPs) are soluble dynamin-like proteins with structured domains that undergo a conformational transition for GTP-controlled oligomerization to exert their function as part of the innate immune system of mammalian cells - attacking intra-cellular parasites by disrupting their membranes. The structural basis and mechanism of this process is unknown. Therefore, we apply neutron spin echo, X-ray scattering, fluorescence, and EPR spectroscopy as techniques for integrative dynamic structural biology to human GBP1 (hGBP1). We mapped hGBP1's essential dynamics from nanoseconds to milliseconds by motional spectra of sub-domains. We find a GTP-independent flexibility of the C-terminal effector domain in the $μ$s-regime and structurally characterize conformers being essential that hGBP1 can open like a pocketknife for oligomerization. This unveils the intrinsic flexibility, a GTP-triggered association of the GTPase-domains and assembly-dependent GTP-hydrolysis as functional design principles of hGBP1 that control its reversible oligomerization in polar assemblies and the subsequent formation of condensates. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2004_04229 |
| institution | arXiv |
| publishDate | 2020 |
| record_format | arxiv |
| spellingShingle | Integrative dynamic structural biology unveils conformers essential for the oligomerization of a large GTPase Peulen, Thomas-Otavio Hengstenberg, Carola S. Biehl, Ralf Dimura, Mykola Lorenz, Charlotte Valeri, Alessandro Ince, Semra Vöpel, Tobias Faragó, Bela Gohlke, Holger Klare, Johann P. Stadler, Andreas M. Seidel, Claus A. M. Herrmann, Christian Biological Physics Biomolecules Guanylate binding proteins (GBPs) are soluble dynamin-like proteins with structured domains that undergo a conformational transition for GTP-controlled oligomerization to exert their function as part of the innate immune system of mammalian cells - attacking intra-cellular parasites by disrupting their membranes. The structural basis and mechanism of this process is unknown. Therefore, we apply neutron spin echo, X-ray scattering, fluorescence, and EPR spectroscopy as techniques for integrative dynamic structural biology to human GBP1 (hGBP1). We mapped hGBP1's essential dynamics from nanoseconds to milliseconds by motional spectra of sub-domains. We find a GTP-independent flexibility of the C-terminal effector domain in the $μ$s-regime and structurally characterize conformers being essential that hGBP1 can open like a pocketknife for oligomerization. This unveils the intrinsic flexibility, a GTP-triggered association of the GTPase-domains and assembly-dependent GTP-hydrolysis as functional design principles of hGBP1 that control its reversible oligomerization in polar assemblies and the subsequent formation of condensates. |
| title | Integrative dynamic structural biology unveils conformers essential for the oligomerization of a large GTPase |
| topic | Biological Physics Biomolecules |
| url | https://arxiv.org/abs/2004.04229 |