2LRI
NMR structure of the second PHD finger of AIRE (AIRE-PHD2)
Summary for 2LRI
| Entry DOI | 10.2210/pdb2lri/pdb |
| NMR Information | BMRB: 18374 |
| Descriptor | Autoimmune regulator, ZINC ION (2 entities in total) |
| Functional Keywords | zn binding protein domain, apeced, transcription |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: O43918 |
| Total number of polymer chains | 1 |
| Total formula weight | 6941.50 |
| Authors | Gaetani, M.,Chignola, F.,Mollica, L.,Quilici, G.,Mannella, V.,Spiliotopoulos, D.,Musco, G. (deposition date: 2012-04-03, release date: 2012-10-17, Last modification date: 2024-05-15) |
| Primary citation | Gaetani, M.,Matafora, V.,Saare, M.,Spiliotopoulos, D.,Mollica, L.,Quilici, G.,Chignola, F.,Mannella, V.,Zucchelli, C.,Peterson, P.,Bachi, A.,Musco, G. AIRE-PHD fingers are structural hubs to maintain the integrity of chromatin-associated interactome. Nucleic Acids Res., 40:11756-11768, 2012 Cited by PubMed Abstract: Mutations in autoimmune regulator (AIRE) gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of peripheral-tissue antigens to mediate deletional tolerance, thereby preventing self-reactivity. AIRE contains two plant homeodomains (PHDs) which are sites of pathological mutations. AIRE-PHD fingers are important for AIRE transcriptional activity and presumably play a crucial role in the formation of multimeric protein complexes at chromatin level which ultimately control immunological tolerance. As a step forward the understanding of AIRE-PHD fingers in normal and pathological conditions, we investigated their structure and used a proteomic SILAC approach to assess the impact of patient mutations targeting AIRE-PHD fingers. Importantly, both AIRE-PHD fingers are structurally independent and mutually non-interacting domains. In contrast to D297A and V301M on AIRE-PHD1, the C446G mutation on AIRE-PHD2 destroys the structural fold, thus causing aberrant AIRE localization and reduction of AIRE target genes activation. Moreover, mutations targeting AIRE-PHD1 affect the formation of a multimeric protein complex at chromatin level. Overall our results reveal the importance of AIRE-PHD domains in the interaction with chromatin-associated nuclear partners and gene regulation confirming the role of PHD fingers as versatile protein interaction hubs for multiple binding events. PubMed: 23074189DOI: 10.1093/nar/gks933 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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