1wd2
Solution Structure of the C-terminal RING from a RING-IBR-RING (TRIAD) motif
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OverviewOverview
The really interesting new gene (RING) family of proteins contains over, 400 members with diverse physiological functions. A subset of these, domains is found in the context of the RING-IBR-RING/TRIAD motifs which, function as E3 ubiquitin ligases. Our sequence analysis of the C-terminal, RING (RING2) from this motif show that several metal ligating and, hydrophobic residues critical for the formation of a classical RING, cross-brace structure are not present. Thus, we determined the structure, of the RING2 from the RING-IBR-RING motif of HHARI and showed that RING2, has a completely distinct topology from classical RINGs. Notably, RING2, binds only one zinc atom per monomer rather than two and uses a different, hydrophobic network to that of classical RINGs. Additionally, this RING2, topology is novel, bearing slight resemblance to zinc-ribbon motifs around, the zinc site and is different from the topologies of the zinc binding, sites found in RING and PHDs. We demonstrate that RING2 acts as an E3, ligase in vitro and using mutational analysis deduce the structural, features required for this activity. Further, mutations in the, RING-IBR-RING of Parkin cause a rare form of Parkinsonism and these, studies provide an explanation for those mutations that occur in its, RING2. From a comparison of the RING2 structure with those reported for, RINGs, we infer sequence determinants that allow discrimination between, RING2 and RING domains at the sequence analysis level.
DiseaseDisease
Known disease associated with this structure: Schizophrenia, susceptibility to OMIM:[142445]
About this StructureAbout this Structure
1WD2 is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Active as Ubiquitin--protein ligase, with EC number 6.3.2.19 Full crystallographic information is available from OCA.
ReferenceReference
Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING., Capili AD, Edghill EL, Wu K, Borden KL, J Mol Biol. 2004 Jul 23;340(5):1117-29. PMID:15236971
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