Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase

Blueggel, Mike; van den Boom, Johannes; Meyer, Hemmo; Bayer, Peter; Beuck, Christine

doi:10.3390/biom9120876

Open AccessArticle

Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase

by

Mike Blueggel

¹

,

Johannes van den Boom

²,

Hemmo Meyer

²,

Peter Bayer

¹

and

Christine Beuck

^1,*

¹

University of Duisburg-Essen, Structural and Medicinal Biochemistry, Centre for Medical Biotechnology (ZMB), 45117 Essen, Germany

²

University of Duisburg-Essen, Molecular Biology, 45117 Essen, Germany

^*

Author to whom correspondence should be addressed.

Biomolecules 2019, 9(12), 876; https://doi.org/10.3390/biom9120876

Submission received: 7 November 2019 / Revised: 11 December 2019 / Accepted: 11 December 2019 / Published: 14 December 2019

(This article belongs to the Section Molecular Structure and Dynamics)

Download

Browse Figures

Versions Notes

Abstract

AAA+ ATPase p97/valosin-containing protein (VCP)/Cdc48 is a key player in various cellular stress responses in which it unfolds ubiquitinated proteins to facilitate their degradation by the proteasome. P97 works in different cellular processes using alternative sets of cofactors and is implicated in multiple degenerative diseases. Ubiquitin regulatory X domain protein 1 (UBXD1) has been linked to pathogenesis and is unique amongst p97 cofactors because it interacts with both termini of p97. Its N-domain binds to the N-domain and N/D1 interface of p97 and regulates its ATPase activity. The PUB (peptide:N-glycanase and UBA or UBX-containing proteins) domain binds the p97 C-terminus, but how it controls p97 function is still unknown. Here we present the NMR structure of UBXD1-PUB together with binding studies, mutational analysis, and a model of UBXD1-PUB in complex with the p97 C-terminus. While the binding pocket is conserved among PUB domains, UBXD1-PUB features a unique loop and turn regions suggesting a role in coordinating interaction with downstream regulators and substrate processing

Keywords: UBXD1; p97/VCP/Cdc48; PUB domain; NMR structure; protein–protein interaction

Graphical Abstract

Share and Cite

MDPI and ACS Style

Blueggel, M.; van den Boom, J.; Meyer, H.; Bayer, P.; Beuck, C. Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase. Biomolecules 2019, 9, 876. https://doi.org/10.3390/biom9120876

AMA Style

Blueggel M, van den Boom J, Meyer H, Bayer P, Beuck C. Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase. Biomolecules. 2019; 9(12):876. https://doi.org/10.3390/biom9120876

Chicago/Turabian Style

Blueggel, Mike, Johannes van den Boom, Hemmo Meyer, Peter Bayer, and Christine Beuck. 2019. "Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase" Biomolecules 9, no. 12: 876. https://doi.org/10.3390/biom9120876

APA Style

Blueggel, M., van den Boom, J., Meyer, H., Bayer, P., & Beuck, C. (2019). Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase. Biomolecules, 9(12), 876. https://doi.org/10.3390/biom9120876

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI