2LRI

NMR structure of the second PHD finger of AIRE (AIRE-PHD2)

2LRI の概要

• エントリーDOI: 10.2210/pdb2lri/pdb
• NMR情報: BMRB: 18374
• 分子名称: Autoimmune regulator, ZINC ION (2 entities in total)
• 機能のキーワード: zn binding protein domain, apeced, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: O43918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6941.50

構造登録者

Gaetani, M.,Chignola, F.,Mollica, L.,Quilici, G.,Mannella, V.,Spiliotopoulos, D.,Musco, G. (登録日: 2012-04-03, 公開日: 2012-10-17, 最終更新日: 2024-05-15)

主引用文献

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

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: 23074189
DOI: 10.1093/nar/gks933

実験手法

SOLUTION NMR