2o96
Crystal Structure of the Metal-Free Dimeric Human Mov34 MPN domain (residues 1-177)
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OverviewOverview
The 26S proteasome is a large protein complex involved in protein, degradation. We have shown previously that the PSMD7/Mov34 subunit of the, human proteasome contains a proteolytically resistant MPN domain. MPN, domain family members comprise subunits of the proteasome, COP9-signalosome and translation initiation factor 3 complexes. Here, the, crystal structure of two C-terminally truncated proteins, MPN 1-186 and, MPN 1-177, were solved to 1.96 and 3.0 A resolution, respectively. MPN, 1-186 is formed by nine beta-strands surrounded by three alpha-helices, plus a fourth alpha-helix at the C terminus. This final alpha-helix, emerges from the domain core and folds along with a symmetrically related, subunit, typical of a domain swap. The crystallographic dimer is, consistent with size-exclusion chromatography and DLS analysis showing, that MPN 1-186 is a dimer in solution. MPN 1-186 shows an overall, architecture highly similar to the previously reported crystal structure, of the Archaeal MPN domain AfJAMM of Archaeoglobus fulgidus. However, previous structural and biophysical analyses have shown that neither MPN, 1-186 nor full-length human Mov34 bind metal, in opposition to the, zinc-binding AfJAMM structures. The zinc ligand residues observed in, AfJAMM are conserved in the yeast Rpn11 proteasome and Csn5, COP-signalosome subunits, which is consistent with the isopeptidase, activity described for these proteins. The results presented here show, that, although the MPN domain of Mov34 shows a typical metalloprotease, fold, it is unable to coordinate a metal ion. This finding and amino acid, sequence comparisons can explain why the MPN-containing proteins, Mov34/PSMD7, RPN8, Csn6, Prp8p and the translation initiation factor 3, subunits f and h do not show catalytic isopeptidase activity, allowing us, to propose the hypothesis that in these proteins the MPN domain has a, primarily structural function.
About this StructureAbout this Structure
2O96 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The Crystal Structure of the Human Mov34 MPN Domain Reveals a Metal-free Dimer., Sanches M, Alves BS, Zanchin NI, Guimaraes BG, J Mol Biol. 2007 Jul 27;370(5):846-55. Epub 2007 May 10. PMID:17559875
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