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Structure. 2017 Jun 6;25(6):823-833.e6. doi: 10.1016/j.str.2017.04.002. Epub 2017 May 4.

Structural Insight into Ubiquitin-Like Protein Recognition and Oligomeric States of JAMM/MPN+ Proteases.

Author information

1
Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA.
2
Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France.
3
Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France. Electronic address: franzetti@ibs.fr.
4
Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA; Genetics Institute, University of Florida, Gainesville, FL 32611, USA. Electronic address: jmaupin@ufl.edu.

Abstract

JAMM/MPN+ metalloproteases cleave (iso)peptide bonds C-terminal to ubiquitin (Ub) and ubiquitin-like protein (Ubl) domains and typically require association with protein partners for activity, which has limited a molecular understanding of enzyme function. To provide an insight, we solved the X-ray crystal structures of a catalytically active Pyrococcus furiosus JAMM/MPN+ metalloprotease (PfJAMM1) alone and in complex with a Ubl (PfSAMP2) to 1.7- to 1.9-Å resolution. PfJAMM1 was found to have a redox sensitive dimer interface. In the PfJAMM1-bound state of the SAMP2, a Ubl-to-Ub conformational change was detected. Surprisingly, distant homologs of PfJAMM1 were found to be closely related in 3D structure, including the interface for Ubl/Ub binding. From this work, we infer the molecular basis of how JAMM/MPN+ proteases recognize and cleave Ubl/Ub tags from diverse proteins and highlight an α2-helix structural element that is conserved and crucial for binding and removing the Ubl SAMP2 tag.

KEYWORDS:

archaea; deubiquitinase; metalloprotease; ubiquitin; ubiquitin-like protein

PMID:
28479062
PMCID:
PMC5831132
DOI:
10.1016/j.str.2017.04.002
[Indexed for MEDLINE]
Free PMC Article

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