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

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. Copyright © 2017 Elsevier Ltd. All rights reserved.

Citation

Shiyun Cao, Sylvain Engilberge, Eric Girard, Frank Gabel, Bruno Franzetti, Julie A Maupin-Furlow. Structural Insight into Ubiquitin-Like Protein Recognition and Oligomeric States of JAMM/MPN+ Proteases. Structure (London, England : 1993). 2017 Jun 06;25(6):823-833.e6

PMID: 28479062

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