The human ATPase p97 (also known as VCP) unfolds protein substrates by translocating them through its central channel. This process is highly regulated by numerous adapter proteins. Structures of p97 in complex with the unusual adapter UBXD1 reveal how this protein coordinates p97 hexamer remodeling and ring opening by expansive interactions across multiple p97 protomers.
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References
Stach, L. & Freemont, P. S. The AAA+ ATPase p97, a cellular multitool. Biochem. J. 474, 2953–2976 (2017). A review of p97 cellular functions and p97 interactions with adapter proteins.
Papadopoulos, C. et al. VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. EMBO J 36, 135–150 (2016). This paper reports that a complex including p97 and UBXD1 is necessary for the clearance of damaged lysosomes through autophagy.
Bento, A. C. et al. UBXD1 is a mitochondrial recruitment factor for p97/VCP and promotes mitophagy. Sci. Rep. 8, 12415 (2018). This paper reports a role for p97 and UBXD1 in clearing damaged mitochondria in Parkin-dependent mitophagy.
Ritz, D. et al. Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations. Nat. Cell. Biol. 13, 1116–1123 (2011). This paper reports that p97 and UBXD1 are necessary for endolysosomal trafficking of cargo proteins.
Blueggel, M. et al. The UBX domain in UBXD1 organizes ubiquitin binding at the C-terminus of the VCP/p97 AAA-ATPase. Nat. Commun. 14, 3258 (2023). This paper reports that the UBX domain in UBXD1 binds ubiquitin, thereby implicating UBXD1 in direct substrate binding.
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This is a summary of: Braxton, J. R. et al. The p97/VCP adapter UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-023-01126-0 (2023).
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Multidomain interactions and ring opening of the p97 ATPase by the UBXD1 adapter. Nat Struct Mol Biol 30, 1842–1843 (2023). https://doi.org/10.1038/s41594-023-01127-z
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DOI: https://doi.org/10.1038/s41594-023-01127-z
