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The human GID complex uses two independent modules for substrate recruitment

Credit: PIXTA / CC0 public domain

A new paper by the Peter group at the ETH Zurich Institute for Biochemistry (IBC) shows that human GID E3 ubiquitin ligase forms a tetramer complex with two different substrate recruitment modules: WDR26-RanBP9 and GID4-ARMC8a. I understand. The shorter ARMC8b isoforms stably assemble into the hGID complex, but lack the ability to recruit GID4 substrate receptors.

Human GID (hGID) complex is conserved E3 Ubiquitin Ligase Regulation of various biological processes including Glucose metabolism And the progress of the cell cycle. However, the biochemical function and substrate recognition of multi-subunit complexes remain poorly understood. Using biochemical assays, cross-linked mass spectrometry, and cryo-electron microscopy, researchers have shown that hGID is involved in two different modules for substrate recruitment, depending on either WDR26 or GID4. I am.

WDR26 and RanBP9 work together to ubiquitinize HBP1 in vitro, but GID4 is essential for this reaction. In contrast, GID4 acts as an adapter for the substrate ZMYND19, which surprisingly lacks the Pro / N-end rule degron. GID4 substrate binding and ligase activity are regulated by ARMC8α, but short ARMC8β isoforms assemble into a stable hGID complex that cannot recruit GID4. Cryogenic electron microscopy reconstruction of these hGID complexes reveals the localization of WDR26 within the ring-shaped tetramer structure, suggesting that GID4 and WDR26 / Gid7 utilize different, non-overlapping binding sites. increase. Together, these data advance our mechanical understanding of how the hGID complex recruits cognate substrates and provide insight into its regulation of E3 ligase activity.

The study is published at EMBO Report..


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For more information:
Weaam I Mohamed et al, Human GID Complex, uses two independent modules for substrate recruitment. EMBO Report (2021). DOI: 10.15252 / embr.202152981

Quote: Human GID Complex is a substrate recruitment obtained on October 25, 2021 from https: //phys.org/news/2021-10-human-gid-complex-engages-independent.html (10 2021) Use two independent modules for May 25th)

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The human GID complex uses two independent modules for substrate recruitment

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