The human GID advanced engages two unbiased modules for substrate recruitment


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A brand new paper by the Peter group of the ETH Zurich’s Institute of Biochemistry (IBC) finds that the human GID E3 ubiquitin ligase types a tetrameric advanced with two distinct substrate-recruitment modules, specifically WDR26-RanBP9 and GID4-ARMC8a. Although the shorter ARMC8b isoform stably assembles into the hGID advanced, it lacks the power to recruit the GID4 substrate-receptor.

The human GID (hGID) advanced is a conserved E3 ubiquitin ligase regulating various organic processes together with glucose metabolism and cell cycle development. However, the biochemical operate and substrate recognition of the multi-subunit advanced stay poorly understood. Using biochemical assays, crosslinking-mass spectrometry and cryo-electron microscopy, the researchers present that hGID engages two distinct modules for substrate recruitment, depending on both WDR26 or GID4.

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WDR26 and RanBP9 cooperate to ubiquitinate HBP1 in vitro, whereas GID4 is dispensable for this response. In distinction, GID4 capabilities as an adaptor for the substrate ZMYND19, which surprisingly lacks a Pro/N-end rule degron. GID4 substrate binding and ligase exercise is regulated by ARMC8α, whereas the shorter ARMC8β isoform assembles right into a steady hGID advanced that’s unable to recruit GID4. Cryo-EM reconstructions of those hGID complexes reveal the localization of WDR26 inside a ring-like, tetrameric structure and recommend that GID4 and WDR26/Gid7 make the most of completely different, non-overlapping binding websites. Together, these information advance our mechanistic understanding of how the hGID advanced recruit cognate substrates and supply insights into the regulation of its E3 ligase exercise.

The examine is printed in EMBO Reports.

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More data:
Weaam I Mohamed et al, The human GID advanced engages two unbiased modules for substrate recruitment, EMBO Reports (2021). DOI: 10.15252/embr.202152981

The human GID advanced engages two unbiased modules for substrate recruitment (2021, October 25)
retrieved 25 October 2021

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