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Molecular recognition of ubiquitin and Lys63-linked diubiquitin by STAM2 UIM-SH3 dual domain: the effect of its linker length and flexibility

Abstract : Multidomain proteins represent a broad spectrum of the protein landscape and are involved in various interactions. They could be considered as modular building blocks assembled in distinct fashion and connected by linkers of varying lengths and sequences. Due to their intrinsic flexibility, these linkers provide proteins a subtle way to modulate interactions and explore a wide range of conformational space. In the present study, we are seeking to understand the effect of the flexibility and dynamics of the linker involved in the STAM2 UIM-SH3 dual domain protein with respect to molecular recognition. We have engineered several constructs of UIM-SH3 with different length linkers or domain deletion. By means of SAXS and NMR experiments, we have shown that the modification of the linker modifies the flexibility and the dynamics of UIM-SH3. Indeed, the global tumbling of both the UIM and SH3 domain is different but not independent from each other while the length of the linker has an impact on the ps-ns time scale dynamics of the respective domains. Finally, the modification of the flexibility and dynamics of the linker has a drastic effect on the interaction of UIM-SH3 with Lys63-linked diubiquitin with a roughly eight-time weaker dissociation constant.
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https://hal.archives-ouvertes.fr/hal-02441244
Contributor : Agnès Bussy <>
Submitted on : Wednesday, January 15, 2020 - 4:35:12 PM
Last modification on : Friday, April 17, 2020 - 3:52:02 PM

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Minh-Ha Nguyen, Marie Martin, Henry Kim, Frank Gabel, Olivier Walker, et al.. Molecular recognition of ubiquitin and Lys63-linked diubiquitin by STAM2 UIM-SH3 dual domain: the effect of its linker length and flexibility. Scientific Reports, Nature Publishing Group, 2019, 9 (1), ⟨10.1038/s41598-019-51182-0⟩. ⟨hal-02441244⟩

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