5lda
From Proteopedia
Structure of deubiquitinating enzyme homolog (Pyrococcus furiosus JAMM1) in complex with ubiquitin-like SAMP2.
Structural highlights
FunctionJAMM1_PYRFU Metalloprotease that displays desampylase (DSAMP) activity, cleaving ubiquitin-like small archaeal modifier proteins (SAMP1, SAMP2 and SAMP3) from protein conjugates (isopeptide- and linear-linked). Thus, likely regulates sampylation and the pools of 'free' SAMP available for protein modification. In vitro, is also able to cleave non-physiological ubiquitin (Ub) substrates, such as 'Met1-', 'Lys48-', and 'Lys63'-linked Ub dimers (Ub2), and to remove Ub tags from diverse proteins.[1] Publication Abstract from PubMedJAMM/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-A 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 alpha2-helix structural element that is conserved and crucial for binding and removing the Ubl SAMP2 tag. Structural Insight into Ubiquitin-Like Protein Recognition and Oligomeric States of JAMM/MPN+ Proteases.,Cao S, Engilberge S, Girard E, Gabel F, Franzetti B, Maupin-Furlow JA Structure. 2017 May 4. pii: S0969-2126(17)30103-X. doi:, 10.1016/j.str.2017.04.002. PMID:28479062[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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