Structure and Function of MPN (Mpr1/Pad1 N-terminal) Domain- Containing Proteins

Author(s): Melissa Birol, Aude Echalier

Journal Name: Current Protein & Peptide Science

Volume 15 , Issue 5 , 2014

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MPN (Mpr1/Pad1 N-terminal) domain-containing proteins are present throughout all domains of life. In eukaryotes, MPN domain-containing proteins are commonly found in association with other molecules in large protein complexes, where examples comprise; the 26S proteasome and the COP9 (Constitutive photomorphogenesis 9) signalosome complexes, including the MPN subunits, POH1 and Mov34, CSN5 and CSN6, respectively. Examples of MPN domaincontaining proteins that are not incorporated in a large multi-protein complex have also been reported and include AMSH (for associated molecule with the SH3 domain of STAM) and the AMSH-Like Protein (AMSH-LP). Within the MPN domain super-family, two main subclasses have been characterised: the MPN+ and MPN- domain-containing proteins. MPN+ domain-containing proteins are classified as metalloenzymes responsible for isopeptidase activity. These proteins display a JAMM (JAB1-MPN-MOV34) metalloisopeptidase motif, typically consisting of a canonical sequence (E-x[2]-H-S/T-Hx[ 7]-S-x[2]-D) and coordinating a zinc ion. The JAMM motif specifies a catalytic centre essential for selective hydrolysis of linkages, contained between ubiquitin/ubiquitin-like proteins and target proteins or between ubiquitin monomers within a polymeric chain. The MPN- family classifies proteins, which lack the key residues present in the typical JAMM motif. These MPN- proteins are void of catalytic activity, but recent studies have proposed a role in mediating protein-protein interactions, in acting as a scaffold or in activity regulation. In light of recent structural and functional studies, a more detailed understanding of these proteins has been gained and is given in the present review.

Keywords: Cell signalling, ubiquitin-proteasome system, isopeptidase activity, COP9 signalosome, Prp8, protein-protein interactions, ubiquitin, Nedd8, CSN.

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Article Details

Year: 2014
Page: [504 - 517]
Pages: 14
DOI: 10.2174/1389203715666140221095109
Price: $65

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